Increased fibroblast chymase production mediates procollagen autophagic digestion in volume overload

Journal of Molecular and Cellular Cardiology
Lianwu FuLouis J Dell'Italia

Abstract

Previous work has identified mast cells as the major source of chymase largely associated with a profibrotic phenotype. We recently reported increased fibroblast autophagic procollagen degradation in a rat model of pure volume overload (VO). Here we demonstrate a connection between increased fibroblast chymase production and autophagic digestion of procollagen in the pure VO of aortocaval fistula (ACF) in the rat. Isolated LV fibroblasts taken from 4 and 12week ACF Sprague-Dawley rats have significant increases in chymase mRNA and chymase activity. Increased intracellular chymase protein is documented by immunocytochemistry in the ACF fibroblasts compared to cells obtained from age-matched sham rats. To implicate VO as a stimulus for chymase production, we show that isolated adult rat LV fibroblasts subjected to 24h of 20% cyclical stretch induces chymase mRNA and protein production. Exogenous chymase treatment of control isolated adult cardiac fibroblasts demonstrates that chymase is internalized through a dynamin-dependent mechanism. Chymase treatment leads to an increased formation of autophagic vacuoles, LC3-II production, autophagic flux, resulting in increased procollagen degradation. Chymase inhibitor treatment reduces c...Continue Reading

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Citations

Apr 10, 2016·Journal of Molecular and Cellular Cardiology·Ashley L EadieKeith R Brunt
Jul 19, 2016·Experimental Physiology·Daniel J Duggan, Reza Tabrizchi
Jan 20, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Richard N Re
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Sep 10, 2017·Journal of Cellular Physiology·Sarfaraz AhmadHao Wang
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Jan 20, 2018·Circulation Research·Louis J Dell'ItaliaCarlos M Ferrario
Oct 4, 2018·Expert Opinion on Therapeutic Patents·Sarfaraz Ahmad, Carlos M Ferrario
Dec 24, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Rachel C ChildersKeith J Gooch
May 29, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Carlos M FerrarioLouis J Dell Italia
Aug 3, 2019·The European Respiratory Journal·Gunnar Pejler
Dec 6, 2019·Frontiers in Cardiovascular Medicine·Carlos M FerrarioJasmina Varagic
Sep 21, 2018·Frontiers in Pharmacology·Martin HoudePedro D'Orléans-Juste
Feb 4, 2019·Molecular and Cellular Biochemistry·Hao WangLeanne Groban
Apr 25, 2018·International Journal of Cardiology·Tiankai LiCarlos M Ferrario

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