Sarco“MiR” friend or foe: a perspective on the mechanisms of doxorubicin-induced cardiomyopathy

Abstract

Anthracyclines are a class of chemotherapeutics used to treat a variety of human cancers including both solid tumors such as breast, ovarian, and lung, as well as malignancies of the blood including leukemia and lymphoma. Despite being extremely effective anti-cancer agents, the application of these drugs is offset by side effects, most notably cardiotoxicity. Many patients treated with doxorubicin (DOX), one of the most common anthracyclines used in oncology, will develop radiographic signs and/or symptoms of cardiomyopathy. Since more and more patients treated with these drugs are surviving their malignancies and manifesting with heart disease, there is particular interest in understanding the mechanisms of anthracycline-induced injury and developing ways to prevent and treat its most feared complication, heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of mRNAs. Since miRNAs can regulate many mRNAs in a single network they tend to play a crucial role in the pathogenesis of several diseases, including heart failure. Here we present a perspective on a recent work by Roca-Alonso and colleagues who demonstrate a cardioprotective function of the miR-30 family members following DOX-induced cardiac injury. They provide evidence for direct targeting of these miRNAs on key elements of the β-adrenergic pathway and further show that this interaction regulates cardiac function and apoptosis. These experiments deliver fresh insights into the biology of toxin-induced cardiomyopathy and suggest the potential for novel therapeutic targets.

Potential Involvement of MiR-30e-3p in Myocardial Injury Induced by Coronary Microembolization via Autophagy Activation

“…The heart can abundantly express miR-30 family members which are widely involved in the pathophysiology of various heart diseases [24-26]. In the field of cardiac research, research on the miR-30 family is mainly focused on myocardial hypertrophy, myocardial infarction, heart failure and ischemia reperfusion injury [27-29]. The miR-30 family also plays an important role in the inhibition of cardiac ischemic injury [30].…”

Protective Effects of ω-3 PUFA in Anthracycline-Induced Cardiotoxicity: A Critical Review

“…Particularly relevant in this context is the inflammatory hypothesis, which considers the activation of the innate immunity and the release of inflammatory cytokines central in the development and progression of the ATC-induced cardiotoxicity [ 102 , 103 , 104 ]. Similarly, it is worth pointing out the modulatory activity of ATC on the expression of several miRNA involved in the epigenetic regulation of different pathways of apoptosis, since ω-3 fatty acids have also been shown to modulate the epigenetic regulation of gene expression [ 7 , 105 , 106 ].…”

Anti-Inflammatory Properties of Menthol and Menthone in Schistosoma mansoni Infection

“…Urogenital schistosomiasis is caused by Schistosoma haematobium and intestinal schistosomiasis can be caused by several species: S. guineensis, S. intercalatum, S. japonicum, S. mansoni , and S. mekongi (World Health Organization, 2015 ). Schistosomiasis pathology results from an immune response against Schistosoma eggs and granulomatous inflammation around the deposited eggs, stimulated by soluble eggs antigen (SEA), mainly in the liver and intestine tissues (Hatz et al, 1998 ; Hams et al, 2013 ) SEA is known to stimulate an immune type 2 response (Th2) leading to the production of IL-4, IL-5, IL-13, and upregulation of immunoglobulin E (IgE) levels and eosinophils (Hams et al, 2013 ).…”