Aortic valve calcification is mediated by a differential response of aortic valve interstitial cells to inflammation

Neil Venardos1, Nicole A Nadlonek1, Qiong Zhan1

  • 1The Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado School of Medicine.

Insights

Aortic valve cells, unlike other heart valve cells, develop an osteogenic phenotype when exposed to inflammation. This specific response in aortic valve cells contributes to calcific aortic stenosis.

Area of Science:

  • Cardiovascular Biology
  • Cellular Pathophysiology
  • Valvular Heart Disease

Background:

  • Calcific aortic stenosis is common, but calcification of other heart valves is rare.
  • Aortic valve interstitial cells (VICs) are implicated in aortic stenosis pathogenesis.
  • Proinflammatory stimulation of aortic VICs causes osteogenic and inflammatory changes.

Purpose of the Study:

  • To compare the osteogenic response of VICs from different heart valves to proinflammatory stimulation.
  • To investigate the role of toll-like receptor 4 (TLR-4) in this response.

Main Methods:

  • Isolated human VICs from aortic, mitral, pulmonary, and tricuspid valves.
  • Stimulated VICs with Lipopolysaccharide (LPS) to activate TLR-4.
  • Analyzed bone morphogenetic protein 2, intercellular adhesion molecule 1, and monocyte chemoattractant protein 1 production.

Main Results:

  • TLR-4 stimulation induced bone morphogenetic protein 2 production exclusively in aortic VICs.
  • Intercellular adhesion molecule 1 production and monocyte chemoattractant protein 1 secretion increased similarly across all stimulated VIC types.
  • Aortic VICs demonstrated a unique osteogenic response to proinflammatory stimuli.

Conclusions:

  • Proinflammatory stimulation triggers an osteogenic phenotype in aortic VICs but not in mitral, pulmonic, or tricuspid VICs.
  • The distinct osteogenic response of aortic VICs is a key factor in the development of calcific aortic stenosis.
Abstract

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