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

Robert M Weiss; Jordan D Miller; Donald D Heistad

doi:10.1161/CIRCRESAHA.113.300153

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

Journal article

Open access

Peer reviewed

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

Robert M Weiss, Jordan D Miller and Donald D Heistad

Circulation research, Vol.113(2), pp.209-222

07/05/2013

DOI: 10.1161/CIRCRESAHA.113.300153

PMCID: PMC3786138

PMID: 23833295

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https://doi.org/10.1161/CIRCRESAHA.113.300153View

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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.

Heart Valve Diseases - pathology

Humans

Heart Defects, Congenital - pathology

Cardiomyopathies - pathology

Bicuspid Aortic Valve Disease

Disease Progression

Aortic Valve - pathology

Cardiomyopathies - therapy

Fibrosis - therapy

Calcinosis - therapy

Animals

Heart Valve Diseases - therapy

Heart Defects, Congenital - therapy

Mice

Fibrosis - pathology

Calcinosis - pathology

Disease Models, Animal

Details

Title: Subtitle: Fibrocalcific aortic valve disease: opportunity to understand disease mechanisms using mouse models
Creators: Robert M Weiss - Division of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA. robert-weiss@uiowa.edu
Jordan D Miller
Donald D Heistad
Resource Type: Journal article
Publication Details: Circulation research, Vol.113(2), pp.209-222
Publisher: United States
DOI: 10.1161/CIRCRESAHA.113.300153
PMID: 23833295
PMCID: PMC3786138
ISSN: 0009-7330
eISSN: 1524-4571
Grant note: HL111121 / NHLBI NIH HHS F32 HL086160 / NHLBI NIH HHS HL62984 / NHLBI NIH HHS R01 HL111121 / NHLBI NIH HHS HL092235 / NHLBI NIH HHS RR026293 / NCRR NIH HHS P01 HL062984 / NHLBI NIH HHS S10 RR026293 / NCRR NIH HHS R00 HL092235 / NHLBI NIH HHS K99 HL092235 / NHLBI NIH HHS HL086160 / NHLBI NIH HHS
Language: English
Date published: 07/05/2013
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040391402771

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