Mitochondrial angiotensin receptors and cardioprotective pathways.

Authors:
Nelson Escobales
Nelson Escobales
School of Medicine
Baltimore | United States
Dr. Sabzali Javadov, MD, PhD, FAHA
Dr. Sabzali Javadov, MD, PhD, FAHA
School of Medicine, University of Puerto Rico, USA
Professor
Cardiology, physiology, biochemistry
San Juan, Puerto Rico | United States

Am J Physiol Heart Circ Physiol 2019 Jun 12;316(6):H1426-H1438. Epub 2019 Apr 12.

Department of Physiology, University of Puerto Rico School of Medicine , San Juan, Puerto Rico.

A growing body of data provides strong evidence that intracellular angiotensin II (ANG II) plays an important role in mammalian cell function and is involved in the pathogenesis of human diseases such as hypertension, diabetes, inflammation, fibrosis, arrhythmias, and kidney disease, among others. Recent studies also suggest that intracellular ANG II exerts protective effects in cells during high extracellular levels of the hormone or during chronic stimulation of the local tissue renin-angiotensin system (RAS). Notably, the intracellular RAS (iRAS) described in neurons, fibroblasts, renal cells, and cardiomyocytes provided new insights into regulatory mechanisms mediated by intracellular ANG II type 1 (ATRs) and 2 (ATRs) receptors, particularly, in mitochondria and nucleus. For instance, ANG II through nuclear ATRs promotes protective mechanisms by stimulating the ATR signaling cascade, which involves mitochondrial ATRs and Mas receptors. The stimulation of nuclear ANG II receptors enhances mitochondrial biogenesis through peroxisome proliferator-activated receptor-γ coactivator-1α and increases sirtuins activity, thus protecting the cell against oxidative stress. Recent studies in ANG II-induced preconditioning suggest that plasma membrane ATR stimulation exerts protective effects against cardiac ischemia-reperfusion by modulating mitochondrial ATR and ATR signaling. These studies indicate that iRAS promotes the protection of cells through nuclear ATR signaling, which, in turn, promotes ATR-dependent processes in mitochondria. Thus, despite abundant data on the deleterious effects of intracellular ANG II, a growing body of studies also supports a protective role for iRAS that could be of relevance to developing new therapeutic strategies. This review summarizes and discusses previous studies on the role of iRAS, particularly emphasizing the protective and counterbalancing actions of iRAS, mitochondrial ANG II receptors, and their implications for organ protection.

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Source
https://www.physiology.org/doi/10.1152/ajpheart.00772.2018
Publisher Site
http://dx.doi.org/10.1152/ajpheart.00772.2018DOI Listing
June 2019
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