Oxidative-mechanical stress signals stem cell niche mediated Lrp5 osteogenesis in eNOS(-/-) null mice.

Journal of Cellular Biochemistry
Nalini M Rajamannan

Abstract

Calcific aortic valve disease (CAVD) is the most common indication for valve surgery in the USA. This study hypothesizes that CAVD develops secondary to Wnt3a/Lrp5 activation via oxidative-mechanical stress in eNOS null mice. eNOS(-/-) mice were tested with experimental diets including a control (n=20), cholesterol (n=20), cholesterol + Atorvastatin (n=20). After 23 weeks the mice were tested for the development of aortic stenosis by Echo, Histology, MicroCT, and RTPCR for bone markers. In vitro studies measured Wnt3a secretion from aortic valve endothelial cells and confirmed oxidative stress via eNOS activity. Anion exchange chromatography was performed to isolate the mitogenic protein. Myofibroblast cells were tested to induce bone formation. Cholesterol treated eNOS mice develop severe stenosis with an increase in Wnt3a, Lrp5, Runx2 (threefold increase (P<0.0001) in the bicuspid versus tricuspid aortic valves. Secretion of Wnt3a from aortic valve endothelium in the presence of abnormal oxidative stress was correlated with diminished eNOS enzymatic activity and tissue nitrite levels. Initial characterization of the architecture for a stem cell nice was determined by protein isolation using anion-exchange chromatography and c...Continue Reading

Citations

May 31, 2014·Mediators of Inflammation·Lia MillucciAnnalisa Santucci
Jan 28, 2014·Journal of Pharmacological Sciences·Ken-Ichi Furukawa
Sep 25, 2018·Journal of Cellular Biochemistry·Nalini M Rajamannan
Jan 29, 2019·Frontiers in Cardiovascular Medicine·Madeleine A GomelK Jane Grande-Allen
Feb 3, 2018·Cardiology·Nalini M Rajamannan

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