Calcific aortic valve stenosis: methods, models, and mechanisms

Circ Res. 2011 May 27;108(11):1392-412. doi: 10.1161/CIRCRESAHA.110.234138.

Abstract

Calcific aortic valve stenosis (CAVS) is a major health problem facing aging societies. The identification of osteoblast-like and osteoclast-like cells in human tissue has led to a major paradigm shift in the field. CAVS was thought to be a passive, degenerative process, whereas now the progression of calcification in CAVS is considered to be actively regulated. Mechanistic studies examining the contributions of true ectopic osteogenesis, nonosseous calcification, and ectopic osteoblast-like cells (that appear to function differently from skeletal osteoblasts) to valvular dysfunction have been facilitated by the development of mouse models of CAVS. Recent studies also suggest that valvular fibrosis, as well as calcification, may play an important role in restricting cusp movement, and CAVS may be more appropriately viewed as a fibrocalcific disease. High-resolution echocardiography and magnetic resonance imaging have emerged as useful tools for testing the efficacy of pharmacological and genetic interventions in vivo. Key studies in humans and animals are reviewed that have shaped current paradigms in the field of CAVS, and suggest promising future areas for research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / pathology*
  • Animals
  • Aortic Valve Stenosis / pathology*
  • Aortic Valve Stenosis / physiopathology*
  • Calcinosis / pathology*
  • Calcinosis / physiopathology*
  • Cell Differentiation / physiology
  • Disease Models, Animal
  • Humans