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Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
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Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro

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Increased dietary intake of vitamin A promotes aortic valve calcification in vivo

Danielle J Huk1, Harriet L Hammond, Hiroyuki Kegechika

  • 1Center for Cardiovascular and Pulmonary Research, Columbus, OH, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 4, 2012
PubMed
Abstract

Insights

Excess vitamin A intake promotes heart valve calcification in mice by affecting gene expression. Hypervitaminosis A may be a new risk factor for calcific aortic valve disease (CAVD).

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Nutritional Science

Background:

  • Calcific aortic valve disease (CAVD) is a prevalent condition with limited treatment options beyond surgery.
  • Previous research linked retinoic acid (RA) treatment to heart valve calcification via Sox9 downregulation.
  • The in vivo and in vitro mechanisms of RA signaling in CAVD remain incompletely understood.

Purpose of the Study:

  • To investigate the impact of excess vitamin A and its metabolite RA on heart valve structure and function in vivo.
  • To elucidate the molecular mechanisms of RA signaling in promoting valve calcification in vitro.

Main Methods:

  • Mice were fed varying doses of retinyl palmitate for 12 months to model excess vitamin A intake.
  • Molecular, cellular, and functional analyses were employed to assess aortic valve pathology.
  • Pharmacological approaches were used to investigate RA signaling pathways, including RA and retinoid X receptors.

Main Results:

  • Excess vitamin A intake induced aortic valve stenosis and leaflet calcification in mice.
  • Observed calcification was associated with upregulated osteogenic genes and downregulated cartilaginous markers.
  • RA-mediated Sox9 repression and subsequent calcification were confirmed to be regulated by classical RA signaling.

Conclusions:

  • Dietary excess of vitamin A promotes heart valve calcification in vivo.
  • Hypervitaminosis A emerges as a potential novel risk factor for calcific aortic valve disease in humans.

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