Faculty Collaboration Database

Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ Res 2006 Jun 09;98(11):1431-8

Date

04/29/2006

Pubmed ID

16645142

DOI

10.1161/01.RES.0000224114.65109.4e

Scopus ID

2-s2.0-33745400942 (requires institutional sign-in at Scopus site)   357 Citations

Abstract

Heart valve disease is an important cause of morbidity and mortality worldwide. Little is known about valve disease pathogenesis, but increasing evidence implicates a genetic basis for valve disease, suggesting a developmental origin. Although the cellular and molecular processes involved in early valvulogenesis have been well described, less is known about the regulation of valve extracellular matrix (ECM) organization and valvular interstitial cell (VIC) distribution that characterize the mature valve structure. Histochemistry, immunohistochemistry, and electron microscopy were used to examine ECM organization, VIC distribution, and cell proliferation during late valvulogenesis in chicken and mouse. In mature valves, ECM organization is conserved across species, and developmental studies demonstrate that ECM stratification begins during late embryonic cusp remodeling and continues into postnatal life. Cell proliferation decreases concomitant with ECM stratification and VIC compartmentalization. Explanted, stenotic bicuspid aortic valves (BAVs) from pediatric patients were also examined. The diseased valves exhibited disruption of the highly organized ECM and VIC distribution seen in normal valves. Cusps from diseased valves were thickened with increased and disorganized collagens and proteoglycans, decreased and fragmented elastic fibers, and cellular disarray without calcification or cell proliferation. Taken together, these studies show that normal valve development is characterized by spatiotemporal coordination of ECM organization and VIC compartmentalization and that these developmental processes are disrupted in pediatric patients with diseased BAVs.

Author List

Hinton RB Jr, Lincoln J, Deutsch GH, Osinska H, Manning PB, Benson DW, Yutzey KE

Author

Joy Lincoln PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aging
Animals
Animals, Newborn
Aortic Valve
Aortic Valve Stenosis
Case-Control Studies
Cell Count
Cell Proliferation
Chickens
Child
Embryo, Mammalian
Embryo, Nonmammalian
Embryonic Development
Extracellular Matrix
Humans
Mice
Rabbits
Sheep