Evidence map›Paper›PMID 27470516›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM.

Ljubica Perisic Matic, Urszula Rykaczewska, Anton Razuvaev, Maria Sabater-Lleal, Mariette Lengquist, Clint L Miller, Ida Ericsson, Samuel Röhl, Malin Kronqvist, Silvia Aldi and 24 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 96 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 1 institution in 4 countries.

Ljubica Perisic MaticFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.). Ljubica.Perisic@ki.se.
Urszula RykaczewskaFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Anton RazuvaevFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Maria Sabater-LlealFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Mariette LengquistFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Clint L MillerFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Ida EricssonFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Samuel RöhlFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Malin KronqvistFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Silvia AldiFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Joelle MagnéFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Valentina PaloschiFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Mattias VesterlundFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Yuhuang LiFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Hong JinFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Maria Gonzalez DiezFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Joy RoyFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Damiano BaldassarreFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Fabrizio VegliaFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Steve E HumphriesFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Ulf de FaireFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Elena TremoliFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Jacob OdebergFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Vladana VukojevićFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Janne LehtiöFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Lars MaegdefesselFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Ewa EhrenborgFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Gabrielle Paulsson-BerneFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Göran K HanssonFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Jan H N LindemanFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Per ErikssonFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Thomas QuertermousFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Anders HamstenFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
Ulf HedinFrom the Departments of Molecular Medicine and Surgery (L.P.M., U.R., A.R., M.L., I.E., S.R., M.K., S.A., J.R., U.H.), Medicine (M.S.-L., J.M., V.P., Y.L., H.J., M.G.D., L.M., E.E., G.P.-B., G.K.H., P.E., A.H.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), and Department of Clinical Neuroscience, Center for Molecular Medicine (V.V.), Karolinska Institutet, Solna, Sweden; Division of Vascular Surgery, Stanford University, CA (C.L.M., T.Q.); Science for Life Laboratory, Solna, Sweden (M.V., J.L.); Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Italy (D.B., E.T.); Dipartimento di Scienze Cliniche e di Comunità, Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.); British Heart Foundation Laboratories, Department of Medicine, University College of London, United Kingdom (S.E.H.); Department of Cardiology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden (U.d.F.); Science for Life Laboratory, Department of Proteomics, Stockholm, Sweden (J.O.); and Department of Vascular Surgery, Leiden University Medical Center, The Netherlands (J.H.N.L.).
MACOM (United States) · US

Funding

Epistatic Regulatory Mechanisms of Coronary Heart Disease RiskK99HL125912 · NHLBI · STANFORD UNIVERSITY · PI MILLER, CLINT L · 2015 to 2016
$285k
British Heart Foundation RG/08/008/25291British Heart Foundation RG2008/014NHLBI NIH HHS K99 HL125912
6 · The paper itself

Abstract

objectiveKey augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability. APPROACH AND

resultsMuscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P<0.0001) and in rat intimal hyperplasia (r>0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation.

conclusionsWe identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation.

Indexed as

Plaque, AtheroscleroticActin CytoskeletonAdaptor Proteins, Signal TransducingAnimalsApolipoproteins EAtherosclerosisAutoantigensCalcium-Binding ProteinsCarotid ArteriesCarotid Artery DiseasesCarotid Artery InjuriesCase-Control StudiesCell DedifferentiationCells, CulturedCytoskeletal ProteinsDisease Models, AnimalAdaptor Proteins, Signal TransducingApolipoproteins EAutoantigensCalcium-Binding ProteinsCytoskeletal ProteinsdesmuslinIntermediate Filament ProteinsLIM Domain ProteinsLMOD1 protein, humanMicrofilament ProteinsPDLIM7 protein, humanPhospholambanSYNPO2 protein, humanactin cytoskeletonatherosclerosisdownregulationhyperplasiasmooth muscle cells

Identifiers

PMID27470516
PMCPMC8991816
OpenAlexW2479301202

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.