HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/H224    most recent 00521.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (30) Citing Articles via Google Scholar Google Scholar Articles by Merryman, W. D. Articles by Sacks, M. S. Search for Related Content PubMed PubMed Citation Articles by Merryman, W. D. Articles by Sacks, M. S.

Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis

¹Engineered Tissue Mechanics Laboratory, Department of Bioengineering and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; ²Orthopaedic Research Laboratories, Departments of Surgery and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina; and ³Collis Cardiac Surgical Research Laboratory, Department of Cardiovascular and Thoracic Surgery, Brown University, Providence, Rhode Island

Submitted 18 May 2005 ; accepted in final form 19 August 2005

It has been speculated that heart valve interstitial cells (VICs) maintain valvular tissue homeostasis through regulated extracellular matrix (primarily collagen) biosynthesis. VICs appear to be phenotypically plastic, inasmuch as they transdifferentiate into myofibroblasts during valve development, disease, and remodeling. Under normal physiological conditions, transvalvular pressures (TVPs) on the right and left side of the heart are vastly different. Hence, we hypothesize that higher left-side TVPs impose larger local tissue stress on VICs, which increases their stiffness through cytoskeletal composition, and that this relation affects collagen biosynthesis. To evaluate this hypothesis, isolated ovine VICs from the four heart valves were subjected to micropipette aspiration to assess cellular stiffness, and cytoskeletal composition and collagen biosynthesis were quantified by using the surrogates smooth muscle -actin (SMA) and heat shock protein 47 (HSP47), respectively. VICs from the aortic and mitral valves were significantly stiffer (P < 0.001) than those from the pulmonary and tricuspid valves. Left-side isolated VICs contained significantly more (P < 0.001) SMA and HSP47 than right-side VICs. Mean VIC stiffness correlated well (r = 0.973) with TVP; SMA and HSP47 also correlated well (r = 0.996) with one another. Assays were repeated for VICs in situ, and, as with in vitro results, left-side VIC protein levels were significantly greater (P < 0.05). These findings suggest that VICs respond to local tissue stress by altering cellular stiffness (through SMA content) and collagen biosynthesis. This functional VIC stress-dependent biosynthetic relation may be crucial in maintaining valvular tissue homeostasis and also prove useful in understanding valvular pathologies.

valve remodeling; cytoskeleton; cell mechanics; micropipette aspiration

This article has been cited by other articles:

				K. Balani, F. C. Brito, L. Kos, and A. Agarwal Melanocyte pigmentation stiffens murine cardiac tricuspid valve leaflet J R Soc Interface, November 6, 2009; 6(40): 1097 - 1102. [Abstract] [Full Text] [PDF]

				I. G. Aldous, S. P. Veres, A. Jahangir, and J. M. Lee Differences in collagen cross-linking between the four valves of the bovine heart: a possible role in adaptation to mechanical fatigue Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1898 - H1906. [Abstract] [Full Text] [PDF]

				A. Itoh, G. Krishnamurthy, J. C. Swanson, D. B. Ennis, W. Bothe, E. Kuhl, M. Karlsson, L. R. Davis, D. C. Miller, and N. B. Ingels Jr. Active stiffening of mitral valve leaflets in the beating heart Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1766 - H1773. [Abstract] [Full Text] [PDF]

				K. Balachandran, P. Sucosky, H. Jo, and A. P. Yoganathan Elevated cyclic stretch alters matrix remodeling in aortic valve cusps: implications for degenerative aortic valve disease Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H756 - H764. [Abstract] [Full Text] [PDF]

				X. Yang, D. A. Fullerton, X. Su, L. Ao, J. C. Cleveland Jr, and X. Meng Pro-osteogenic phenotype of human aortic valve interstitial cells is associated with higher levels of Toll-like receptors 2 and 4 and enhanced expression of bone morphogenetic protein 2. J. Am. Coll. Cardiol., February 10, 2009; 53(6): 491 - 500. [Abstract] [Full Text] [PDF]

				M. S Sacks and A. P Yoganathan Heart valve function: a biomechanical perspective Phil Trans R Soc B, July 27, 2008; 363(1502): 2481 - 2481. [Full Text] [PDF]

				W. D. Merryman Insights Into (the Interstitium of) Degenerative Aortic Valve Disease J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1415 - 1415. [Full Text] [PDF]

				M. Pho, W. Lee, D. R. Watt, C. Laschinger, C. A. Simmons, and C. A. McCulloch Cofilin is a marker of myofibroblast differentiation in cells from porcine aortic cardiac valves Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1767 - H1778. [Abstract] [Full Text] [PDF]

				M. S Sacks and A. P Yoganathan Heart valve function: a biomechanical perspective Phil Trans R Soc B, August 29, 2007; 362(1484): 1369 - 1391. [Abstract] [Full Text] [PDF]

				A. H Chester and P. M Taylor Molecular and functional characteristics of heart-valve interstitial cells Phil Trans R Soc B, August 29, 2007; 362(1484): 1437 - 1443. [Abstract] [Full Text] [PDF]

				B. B. Keller New Insights Into the Developmental Biomechanics of the Atrioventricular Valves Circ. Res., May 25, 2007; 100(10): 1399 - 1401. [Full Text] [PDF]