Evidence map›Paper›PMID 24925974›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Lim domain binding 2: a key driver of transendothelial migration of leukocytes and atherosclerosis.

Ming-Mei Shang, Husain A Talukdar, Jennifer J Hofmann, Colin Niaudet, Hassan Foroughi Asl, Rajeev K Jain, Aranzazu Rossignoli, Cecilia Cedergren, Angela Silveira, Bruna Gigante and 11 more

Abstract read
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  13. Systems Biology and Noninvasive Imaging of Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2016
    Review
  14. Monocyte trafficking across the vessel wall.Cardiovascular research · 2015
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Ming-Mei ShangFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Husain A TalukdarFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Jennifer J HofmannFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Colin NiaudetFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Hassan Foroughi AslFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Rajeev K JainFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Aranzazu RossignoliFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Cecilia CedergrenFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Angela SilveiraFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Bruna GiganteFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Karin LeanderFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Ulf de FaireFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Anders HamstenFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Arno RuusaleppFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Olle MelanderFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Torbjörn IvertFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Tom MichoelFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Eric E SchadtFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Christer BetsholtzFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Josefin SkogsbergFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
Johan L M BjörkegrenFrom the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.). johan.bjorkegren@ki.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveUsing a multi-tissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in a CAD vascular wall regulatory gene network. Here, we used human genomics and atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and atherosclerosis. APPROACH AND

resultsmRNA profiles generated from blood macrophages in patients with CAD were used to infer transcription factor regulatory gene networks; Ldlr(-/-)Apob(100/100) mice were used to study the effects of Ldb2 deficiency on TEML activity and atherogenesis. LDB2 was the most connected gene in a transcription factor regulatory network inferred from TEML and atherosclerosis module genes in CAD macrophages. In Ldlr(-/-)Apob(100/100) mice, loss of Ldb2 increased atherosclerotic lesion size ≈2-fold and decreased plaque stability. The exacerbated atherosclerosis was caused by increased TEML activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In THP1 cells, migration was increased by overexpression and decreased by small interfering RNA inhibition of LDB2. A functional LDB2 variant (rs10939673) was associated with the risk and extent of CAD across several cohorts.

conclusionsAs a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate to target CAD by inhibiting the overall activity of TEML.

Indexed as

AnimalsApolipoprotein B-100AtherosclerosisCarotid Artery DiseasesCell Line, TumorChemokine CCL2Chemotaxis, LeukocyteCoronary Artery DiseaseGene Expression ProfilingGene Expression RegulationGenome-Wide Association StudyHumansLIM Domain ProteinsMacrophagesMiceMice, KnockoutApolipoprotein B-100Chemokine CCL2LDB2 protein, humanLdb2 protein, mouseLIM Domain ProteinsRNA, MessengerTranscription Factorsatherosclerosiscoronary artery diseasegene regulatory networks

Identifiers

PMID24925974

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