Abstract 20908: Notch Signalling in Pathogenesis of Calcified Aortic Valve
Introduction: Calcific aortic valve stenosis (CAVS) is the most common form of acquired valvular disease. A progressive mineralization of aortic valve leaflets is a major culprit in the development of CAVS. CAVS was believed to be a passive degenerative disease, but recent research has shown that it is actually an active, complex inflammatory-like process, reminding atherosclerosis. Cumulative evidence from recent studies shows that loss-of-function polymorphisms and mutations in NOTCH1 are strongly associated with early calcification of aortic valves in humans, but the role of Notch signaling and the mechanisms that may contribute to CAVS remains unknown.
Hypothesis: The aim of the study was to assess the expression level of Notch signaling components and osteogenic differentiation genes in human aortic valvular interstitial cells (VIC) and in human aortic valvular endothelial cells (VEC) derived from the CAVS patients and to assess relationship between clinical and laboratory characteristics of the patients and expression level of Notch signaling components and osteogenic differentiation genes.
Methods: We included 68 patients with CAVS operated in Almazov centre: 32 of them had tricuspid aortic valve (TAV), 6 of which had moderate AS, and 26 had severe AS; 36 of them have bicuspid aortic valve (BAV), 2 of which had moderate AS and 34 had severe AS. The mean ± SD age of patients was 62.09±5.64 in the TAV group and 59.0±8.0 in the BAV group. There were 10 healthy donors, whose cusps were used as controls. VICs were isolated from BAV and TAV cusps from patients with CAVS and from healthy donors. The baseline level of Notch receptors, ligands and target genes was estimated by qPCR.
Results: VICs from BAV group had significantly different levels of Notch signaling components comparing to TAV group and donors, moreover BAV group had significantly different levels of osteogenic differentiation genes comparing to donors.
Conclusions: Our results show that Notch signaling is differently altered in VICs from BAV and TAV patients with CAVS. The observed down regulation of Notch components in valvular interstitial cells in BAV group suggests that Notch signaling is directly involved in the pathogenesis of CAVS.
Author Disclosures: A. Malashicheva: None. A. Shishkova: None. V. Uspenskiy: None. O. Irtyuga: None. O. Moiseeva: None. E. Shlyakhto: None.
- © 2016 by American Heart Association, Inc.