Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 182, Issue 5, Pages 1922-1931Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2013.01.037
Keywords
-
Categories
Funding
- American Heart Association [0830384N]
- Hartwell Foundation
- NIH [HL110328]
- National Science Foundation [CBET-0955172]
- Leducq Foundation
- Magdi Yacoub Institute
- Canadian Institutes of Health Research [MFE-83809]
Ask authors/readers for more resources
Arterial endothelial cells maintain vascular homeostasis and vessel tone in part through the secretion of nitric oxide (NO). In this study, we determined how aortic valve endothelial cells (VEC) regulate aortic valve interstitial cell (VIC) phenotype and matrix calcification through NO. Using an anchored in vitro collagen hydrogel culture system, we demonstrate that three-dimensionally cultured porcine VIC do not calcify in osteogenic medium unless under mechanical stress. Co-culture with porcine VEC, however, significantly attenuated VIC calcification through inhibition of myofibroblastic activation, osteogenic differentiation, and calcium deposition. Incubation with the NO donor DETA-NO inhibited VIC osteogenic differentiation and matrix calcification, whereas incubation with the NO blocker L-NAME augmented calcification even in 3D VIC-VEC co-culture. Aortic VEC, but not VIC, expressed endothelial NO synthase (eNOS) in both porcine and human valves, which was reduced in osteogenic medium. eNOS expression was reduced in calcified human aortic valves in a side-specific manner. Porcine Leaflets exposed to the soluble guanylyl cyclase inhibitor ODQ increased osteocalcin and alpha-smooth muscle actin expression. Finally, side-specific shear stress applied to porcine aortic valve leaflet endothelial surfaces increased cGMP production in VEC. Valve endothelial-derived NO is a natural inhibitor of the early phases of valve calcification and therefore may be an important regulator of valve homeostasis and pathology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available