Evidence map›Paper›PMID 28778947›Full record

ArticleCirculation2017

Disturbed Flow Promotes Arterial Stiffening Through Thrombospondin-1.

Chan Woo Kim, Anastassia Pokutta-Paskaleva, Sandeep Kumar, Lucas H Timmins, Andrew D Morris, Dong-Won Kang, Sidd Dalal, Tatiana Chadid, Katie M Kuo, Julia Raykin and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 5% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

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  15. Endothelial cell (EC)-specific Ctgf/Ccn2 expression increases EC reprogramming and atherosclerosis.Matrix biology : journal of the International Society for Matrix Biology · 2025
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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

15 authors at 6 institutions in 3 countries.

Chan Woo KimFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Anastassia Pokutta-PaskalevaFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Sandeep KumarFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Lucas H TimminsFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Andrew D MorrisFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Dong-Won KangFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Sidd DalalFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Tatiana ChadidFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Katie M KuoFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Julia RaykinFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Haiyan LiFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Hiromi YanagisawaFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Rudolph L GleasonFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
Hanjoong JoFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.). lbrewst@emory.edu luke.brewster@va.gov hjo@emory.edu.
Luke P BrewsterFrom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.). lbrewst@emory.edu luke.brewster@va.gov hjo@emory.edu.
University of Tsukuba · JPEmory University · USGeorgia Institute of Technology · USAtlanta VA Medical Center · USMercer University · USUniversity of Utah · US

Funding

T cell triggering events and hypertensionP01HL095070 · NHLBI · EMORY UNIVERSITY · PI HILENSKI, LULA LAIL · 2009 to 2019
$20.5M
Shear stress, endothelial miRNAs, and AV calcificationR01HL119798 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG, YOGANATHAN, AJIT P · 2013 to 2022
$4.7M
Image-based analysis of miRNA deliveryR01HL124879 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FERRARA, KATHERINE W, JO, HANJOONG · 2014 to 2017
$3.1M
Molecular Mechanism of Disturbed Flow in Arterial StiffeningK08HL119592 · NHLBI · EMORY UNIVERSITY · PI BREWSTER, LUKE PACKARD · 2014 to 2018
$690k
NHLBI NIH HHS K08 HL119592NHLBI NIH HHS P01 HL095070NHLBI NIH HHS R01 HL119798NHLBI NIH HHS R01 HL124879
6 · The paper itself

Abstract

backgroundArterial stiffness and wall shear stress are powerful determinants of cardiovascular health, and arterial stiffness is associated with increased cardiovascular mortality. Low and oscillatory wall shear stress, termed disturbed flow (d-flow), promotes atherosclerotic arterial remodeling, but the relationship between d-flow and arterial stiffness is not well understood. The objective of this study was to define the role of d-flow on arterial stiffening and discover the relevant signaling pathways by which d-flow stiffens arteries.

methodsD-flow was induced in the carotid arteries of young and old mice of both sexes. Arterial stiffness was quantified ex vivo with cylindrical biaxial mechanical testing and in vivo from duplex ultrasound and compared with unmanipulated carotid arteries from 80-week-old mice. Gene expression and pathway analysis was performed on endothelial cell-enriched RNA and validated by immunohistochemistry. In vitro testing of signaling pathways was performed under oscillatory and laminar wall shear stress conditions. Human arteries from regions of d-flow and stable flow were tested ex vivo to validate critical results from the animal model.

resultsD-flow induced arterial stiffening through collagen deposition after partial carotid ligation, and the degree of stiffening was similar to that of unmanipulated carotid arteries from 80-week-old mice. Intimal gene pathway analyses identified transforming growth factor-β pathways as having a prominent role in this stiffened arterial response, but this was attributable to thrombospondin-1 (TSP-1) stimulation of profibrotic genes and not changes to transforming growth factor-β. In vitro and in vivo testing under d-flow conditions identified a possible role for TSP-1 activation of transforming growth factor-β in the upregulation of these genes. TSP-1 knockout animals had significantly less arterial stiffening in response to d-flow than wild-type carotid arteries. Human arteries exposed to d-flow had similar increases TSP-1 and collagen gene expression as seen in our model.

conclusionsTSP-1 has a critical role in shear-mediated arterial stiffening that is mediated in part through TSP-1's activation of the profibrotic signaling pathways of transforming growth factor-β. Molecular targets in this pathway may lead to novel therapies to limit arterial stiffening and the progression of disease in arteries exposed to d-flow.

Indexed as

AgingAnimalsAtrial RemodelingCarotid ArteriesCell LineCollagenDisease Models, AnimalDown-RegulationEndothelium, VascularFemaleHumansImmunohistochemistryMaleMiceMice, Inbred C57BLMice, KnockoutCollagenProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IRNA, Ribosomal, 18SThrombospondin 1Transforming Growth Factor betadisturbed flowthrombospondinsvascular stiffness

Identifiers

PMID28778947
PMCPMC5614852
OpenAlexW2742615982

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.