Autophagy Negatively Regulates Pro-osteogenic Activity in Human Aortic Valve Interstitial Cells

Overview

Journal J Surg Res

Specialty General Surgery

Date 2017 Oct 8

PMID 28985862

Citations 11

Authors

Xin-Sheng Deng

Xianzhong Meng

Neil Venardos

Rui Song

Katsuhiro Yamanaka

David Fullerton

James Jaggers

Affiliations

Soon will be listed here.

Abstract

Background: Autophagy is a physiological process that plays an important role in maintaining cellular functions. When aortic valve interstitial cells (AVICs) are stimulated with inflammatory or mechanical stress, one response is elevated pro-osteogenic activity. We hypothesized that autophagy is important in the prevention or regulation of this pro-osteogenic activity in AVICs.

Materials And Methods: AVICs were isolated. Autophagy activity was examined and its role in AVIC's pro-osteogenic activity was determined using chemical inhibitors and genetic techniques. The pro-osteogenic biomarker bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) were analyzed by immunoblotting and calcium deposition assay.

Results: Human AVICs from normal aortic valve donors displayed significantly higher autophagic activity than those from calcified aortic valve donors as indicated by lower protein levels of light chain 3-II. Suppression of autophagy by 3-methyladenine, bafilomycin, or knockdown of Atg7 gene induced the expression of BMP-2 and ALP, increased ALP activity, and calcium deposit formation in normal AVICs. Conversely, upregulation of autophagy with rapamycin or overexpression of Atg7 gene decreased the levels of BMP-2 and ALP in diseased AVICs.

Conclusions: Our data showed that autophagy negatively regulates the pro-osteogenic activity in human AVICs, suggesting that upregulation of autophagy may prevent the progression of calcific aortic valve disease.

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