Fibrocalcific aortic valve disease: Opportunity to understand disease mechanisms using mouse models

Robert M. Weiss, Jordan D Miller, Donald D. Heistad

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Studies in vitro and in vivo continue to identify complex-regulated mechanisms leading to overt fibrocalcific aortic valve disease (FCAVD). Assessment of the functional impact of those processes requires careful studies of models of FCAVD in vivo. Although the genetic basis for FCAVD is unknown for most patients with FCAVD, several disease-associated genes have been identified in humans and mice. Some gene products which regulate valve development in utero also protect against fibrocalcific disease during postnatal aging. Valve calcification can occur via processes that resemble bone formation. But valve calcification can also occur by nonosteogenic mechanisms, such as formation of calcific apoptotic nodules. Anticalcific interventions might preferentially target either osteogenic or nonosteogenic calcification. Although FCAVD and atherosclerosis share several risk factors and mechanisms, there are fundamental differences between arteries and the aortic valve, with respect to disease mechanisms and responses to therapeutic interventions. Both innate and acquired immunity are likely to contribute to FCAVD. Angiogenesis is a feature of inflammation, but may also contribute independently to progression of FCAVD, possibly by actions of pericytes that are associated with new blood vessels. Several therapeutic interventions seem to be effective in attenuating the development of FCAVD in mice. Therapies which are effective early in the course of FCAVD, however, are not necessarily effective in established disease.

Original languageEnglish (US)
Pages (from-to)209-222
Number of pages14
JournalCirculation Research
Volume113
Issue number2
DOIs
StatePublished - Jul 5 2013

Fingerprint

Aortic Diseases
Aortic Valve
Pericytes
Adaptive Immunity
Innate Immunity
Osteogenesis
Genes
Blood Vessels
Atherosclerosis
Therapeutics
Arteries
Inflammation

Keywords

  • aortic valve
  • aortic valve calcification
  • aortic valve stenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Fibrocalcific aortic valve disease : Opportunity to understand disease mechanisms using mouse models. / Weiss, Robert M.; Miller, Jordan D; Heistad, Donald D.

In: Circulation Research, Vol. 113, No. 2, 05.07.2013, p. 209-222.

Research output: Contribution to journalArticle

Weiss, Robert M. ; Miller, Jordan D ; Heistad, Donald D. / Fibrocalcific aortic valve disease : Opportunity to understand disease mechanisms using mouse models. In: Circulation Research. 2013 ; Vol. 113, No. 2. pp. 209-222.
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