Human interstitial cellular model in therapeutics of heart valve calcification

Amino Acids. 2017 Dec;49(12):1981-1997. doi: 10.1007/s00726-017-2432-3. Epub 2017 May 23.

Abstract

Calcific aortic valve disease is a common, severe heart condition that is currently with no proven, effective drug treatment and requires a surgical valve replacement or an entire heart explanation. Thus, developing novel, targeted therapeutic approaches becomes a major goal for cardiovascular disease research. To achieve this goal, isolated heart valve interstitial cells could be an advanced model to explore molecular mechanisms and measure drug efficacy. Based on this progress, molecular mechanisms that harbor components of inflammation and fibrosis coupled with proteins, for example, BMP-2, TLRs, RANKL, Osteoprotegerin, have been proposed. Small molecules or antibodies targeting these proteins have shown promising efficacy for either reversing or slowing down calcification development in vitro. In this review, we summarize these potential therapeutics with some highlights of interstitial cellular models.

Keywords: BMP-2; Heart valve interstitial cells; Osteoprotegerin; RANKL; TLRs; Valve calcification.

Publication types

  • Review

MeSH terms

  • Animals
  • Aortic Valve / cytology
  • Aortic Valve / pathology*
  • Aortic Valve / physiopathology
  • Aortic Valve Stenosis* / drug therapy
  • Aortic Valve Stenosis* / physiopathology
  • Biomarkers, Pharmacological / metabolism
  • Calcinosis* / drug therapy
  • Calcinosis* / physiopathology
  • Drug Discovery
  • Fibrosis / metabolism
  • Fibrosis / physiopathology
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Models, Biological*
  • Signal Transduction / physiology

Substances

  • Biomarkers, Pharmacological

Supplementary concepts

  • Aortic Valve, Calcification of