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Communication

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

1
Department of Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden
2
Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden
3
Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, 171 77 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1486; https://doi.org/10.3390/ijms20061486
Received: 28 February 2019 / Revised: 18 March 2019 / Accepted: 22 March 2019 / Published: 25 March 2019
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. View Full-Text
Keywords: autophagy; calcification; calcific aortic valve stenosis; valvular interstitial autophagy; calcification; calcific aortic valve stenosis; valvular interstitial
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MDPI and ACS Style

Carracedo, M.; Persson, O.; Saliba-Gustafsson, P.; Artiach, G.; Ehrenborg, E.; Eriksson, P.; Franco-Cereceda, A.; Bäck, M. Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells. Int. J. Mol. Sci. 2019, 20, 1486. https://doi.org/10.3390/ijms20061486

AMA Style

Carracedo M, Persson O, Saliba-Gustafsson P, Artiach G, Ehrenborg E, Eriksson P, Franco-Cereceda A, Bäck M. Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells. International Journal of Molecular Sciences. 2019; 20(6):1486. https://doi.org/10.3390/ijms20061486

Chicago/Turabian Style

Carracedo, Miguel, Oscar Persson, Peter Saliba-Gustafsson, Gonzalo Artiach, Ewa Ehrenborg, Per Eriksson, Anders Franco-Cereceda, and Magnus Bäck. 2019. "Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells" International Journal of Molecular Sciences 20, no. 6: 1486. https://doi.org/10.3390/ijms20061486

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