Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells

被引:23
|
作者
Carracedo, Miguel [1 ]
Persson, Oscar [1 ]
Saliba-Gustafsson, Peter [1 ]
Artiach, Gonzalo [1 ]
Ehrenborg, Ewa [1 ]
Eriksson, Per [1 ]
Franco-Cereceda, Anders [2 ,3 ]
Back, Magnus [1 ,3 ]
机构
[1] Karolinska Inst, Dept Med, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden
[3] Karolinska Univ Hosp, Div Valvular & Coronary Dis, Theme Heart & Vessels, S-17177 Stockholm, Sweden
关键词
autophagy; calcification; calcific aortic valve stenosis; valvular interstitial; EXPRESSION; DEATH;
D O I
10.3390/ijms20061486
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autophagy serves as a cell survival mechanism which becomes dysregulated under pathological conditions and aging. Aortic valve thickening and calcification causing left ventricular outflow obstruction is known as calcific aortic valve stenosis (CAVS). CAVS is a chronic and progressive disease which increases in incidence and severity with age. Currently, no medical treatment exists for CAVS, and the role of autophagy in the disease remains largely unexplored. To further understand the role of autophagy in the progression of CAVS, we analyzed expression of key autophagy genes in healthy, thickened, and calcified valve tissue from 55 patients, and compared them with nine patients without significant CAVS, undergoing surgery for aortic regurgitation (AR). This revealed a upregulation in autophagy exclusively in the calcified tissue of CAVS patients. This difference in autophagy between CAVS and AR was explored by LC3 lipidation in valvular interstitial cells (VICs), revealing an upregulation in autophagic flux in CAVS patients. Inhibition of autophagy by bafilomycin-A1 led to a decrease in VIC survival. Finally, treatment of VICs with high phosphate led to an increase in autophagic activity. In conclusion, our data suggests that autophagy is upregulated in the calcified tissue of CAVS, serving as a compensatory and pro-survival mechanism.
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页数:8
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