Sun L, Sucosky P. Bone morphogenetic protein-4 and transforming growth factor-beta1 mechanisms in acute valvular response to supra-physiologic hemodynamic stresses. World J Cardiol 2015; 7(6): 331-343 [PMID: 26131338 DOI: 10.4330/wjc.v7.i6.331]
Corresponding Author of This Article
Philippe Sucosky, PhD, FAHA, Department of Aerospace and Mechanical Engineering, University of Notre Dame, 143 Multidisciplinary Research Building, Notre Dame, IN 46556-5637, United States. philippe.sucosky@nd.edu
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Basic Study
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Sun L, Sucosky P. Bone morphogenetic protein-4 and transforming growth factor-beta1 mechanisms in acute valvular response to supra-physiologic hemodynamic stresses. World J Cardiol 2015; 7(6): 331-343 [PMID: 26131338 DOI: 10.4330/wjc.v7.i6.331]
World J Cardiol. Jun 26, 2015; 7(6): 331-343 Published online Jun 26, 2015. doi: 10.4330/wjc.v7.i6.331
Bone morphogenetic protein-4 and transforming growth factor-beta1 mechanisms in acute valvular response to supra-physiologic hemodynamic stresses
Ling Sun, Philippe Sucosky
Ling Sun, Philippe Sucosky, Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, United States
Author contributions: Sun L performed the experiments and analyzed the data; Sun L and Sucosky P designed the research and wrote the paper.
Supported by American Heart Association Scientist Development Grant, No. 11SDG7600103.
Conflict-of-interest: The authors declare no conflict of interest.
Data sharing: Complete dataset and statistical analyses available from the corresponding author at philippe.sucosky@nd.edu.
Correspondence to: Philippe Sucosky, PhD, FAHA, Department of Aerospace and Mechanical Engineering, University of Notre Dame, 143 Multidisciplinary Research Building, Notre Dame, IN 46556-5637, United States. philippe.sucosky@nd.edu
Telephone: +1-574-6311898 Fax: +1-574-6312144
Received: January 20, 2015 Peer-review started: January 21, 2015 First decision: February 7, 2015 Revised: February 20, 2015 Accepted: April 16, 2015 Article in press: April 20, 2015 Published online: June 26, 2015 Processing time: 155 Days and 16.9 Hours
Core Tip
Core tip: Although flow abnormalities have been shown to promote valvular pathogenesis in a bone morphogenetic protein-4 (BMP-4)- and transforming growth factor-beta1 (TGF-β1)-dependent manner, the mode of action of those molecules in response to fluid shear stress (FSS) abnormalities remains unknown. This ex vivo study aimed at isolating the role played by those cytokines in the acute response of porcine leaflets to supra-physiologic FSS magnitude/frequency. The study reveals that: (1) valvular endothelial activation is weakly regulated by BMP-4 in response to FSS abnormalities; (2) TGF-β1 silencing attenuates FSS-induced extracellular matrix degradation via MMP-9 downregulation; and (3) BMP-4 and TGF-β1 do not synergistically interact in response to FSS abnormalities.
