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


Journal Article

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 alpha-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.

Full Text

Cited Authors

  • Merryman, WD; Youn, I; Lukoff, HD; Krueger, PM; Guilak, F; Hopkins, RA; Sacks, MS

Published Date

  • January 2006

Published In

Volume / Issue

  • 290 / 1

Start / End Page

  • H224 - H231

PubMed ID

  • 16126816

Pubmed Central ID

  • 16126816

Electronic International Standard Serial Number (EISSN)

  • 1522-1539

International Standard Serial Number (ISSN)

  • 0363-6135

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.00521.2005


  • eng