Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy.

Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy. Circ Res. 2020 Mar 27;126(7):926-941 Authors: Wallace KB, Sardão VA, Oliveira PJ Abstract Anthracycline-based chemotherapy can result in the development of a cumulative and progressively developing cardiomyopathy. Doxorubicin is one of the most highly prescribed anthracyclines in the United States due to its broad spectrum of therapeutic efficacy. Interference with different mitochondrial processes is chief among the molecular and cellular determinants of doxorubicin cardiotoxicity, contributing to the development of cardiomyopathy. The present review provides the basis for the involvement of mitochondrial toxicity in the different functional hallmarks of anthracycline toxicity. Our objective is to understand the molecular determinants of a progressive deterioration of functional integrity of mitochondria that establishes a historic record of past drug treatments (mitochondrial memory) and renders the cancer patient susceptible to subsequent regimens of drug therapy. We focus on the involvement of doxorubicin-induced mitochondrial oxidative stress, disruption of mitochondrial oxidative phosphorylation, and permeability transition, contributing to altered metabolic and redox circuits in cardiac cells, ultimately culminating in disturbances of autophagy/mitophagy fluxes and increased apoptosis. We also suggest some possible pharmacological and nonpharmacological interve...
Source: Circulation Research - Category: Cardiology Authors: Tags: Circ Res Source Type: research