The elastic properties of valve interstitial cells undergoing pathological differentiation

J Biomech. 2012 Mar 15;45(5):882-7. doi: 10.1016/j.jbiomech.2011.11.030. Epub 2011 Dec 19.

Abstract

Increasing evidence indicates that the progression of calcific aortic valve disease (CAVD) is influenced by the mechanical forces experienced by valvular interstitial cells (VICs) embedded within the valve matrix. The ability of VICs to sense and respond to tissue-level mechanical stimuli depends in part on cellular-level biomechanical properties, which may change with disease. In this study, we used micropipette aspiration to measure the instantaneous elastic modulus of normal VICs and of VICs induced to undergo pathological differentiation in vitro to osteoblast or myofibroblast lineages on compliant and stiff collagen gels, respectively. We found that VIC elastic modulus increased after subculturing on stiff tissue culture-treated polystyrene and with pathological differentiation on the collagen gels. Fibroblast, osteoblast, and myofibroblast VICs had distinct cellular-level elastic properties that were not fully explained by substrate stiffness, but were correlated with α-smooth muscle actin expression levels. C-type natriuretic peptide, a peptide expressed in aortic valves in vivo, prevented VIC stiffening in vitro, consistent with its ability to inhibit α-smooth muscle actin expression and VIC pathological differentiation. These data demonstrate that VIC phenotypic plasticity and mechanical adaptability are linked and regulated both biomechanically and biochemically, with the potential to influence the progression of CAVD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Aortic Valve / metabolism
  • Aortic Valve / pathology*
  • Biomechanical Phenomena / physiology
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Collagen / metabolism
  • Elastic Modulus / physiology*
  • Heart Valve Diseases / metabolism
  • Heart Valve Diseases / pathology*
  • Mechanical Phenomena
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology*
  • Natriuretic Peptide, C-Type / metabolism
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Stress, Mechanical
  • Swine

Substances

  • Actins
  • Natriuretic Peptide, C-Type
  • Collagen