Pharmacological inhibition of the mitochondrial NADPH oxidase 4/PKCα/Gal-3 pathway reduces left ventricular fibrosis following myocardial infarction

Translational Research : the Journal of Laboratory and Clinical Medicine
Maria Del Carmen Asensio-LopezDomingo A Pascual-Figal

Abstract

Although the initial reparative fibrosis after myocardial infarction (MI) is crucial for preventing rupture of the ventricular wall, an exaggerated fibrotic response and reactive fibrosis outside the injured area are detrimental. Although metformin prevents adverse cardiac remodeling, as well as provides glycemic control, the underlying mechanisms remain poorly documented. This study describes the effect of mitochondrial NADPH oxidase 4 (mitoNox) and protein kinase C-alpha (PKCα) on the cardiac fibrosis and galectin 3 (Gal-3) expression. Randomly rats underwent MI, received metformin or saline solution. A model of biomechanical strain and co-culturewas used to enable cross talk between cardiomyocytes and fibroblasts. Long-term metformin treatment after MIwas associated with (1) a reduction in myocardial fibrosis and Gal-3 levels; (2) an increase in adenosine monophosphate-activated protein kinase (AMPK) α1/α2 levels; and (3) an inhibition of both mRNA expression and enzymatic activities of mitoNox and PKCα. These findings were replicated in the cellular model, where the silencing of AMPK expression blocked the ability of metformin to protect cardiomyocytes from strain. The use of specific inhibitors or small interference RNA pr...Continue Reading

Citations

Jul 25, 2019·Transplantation·Can-Xiang LinJun-Meng Zheng
Mar 5, 2020·Antioxidants & Redox Signaling·Karen Bernard, Victor J Thannickal
Aug 13, 2020·Scientific Reports·Maria Del Carmen Asensio LopezDomingo A Pascual Figal
Dec 23, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gang WangMao Luo
Feb 18, 2021·Scientific Reports·Maria Carmen Asensio-LopezAntonio Lax
Mar 7, 2021·Free Radical Biology & Medicine·Alice MarinoChristophe Beauloye
May 20, 2021·Journal of Diabetes Research·Maoyan WuYong Xu

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