Viruses are an underappreciated cause of heart failure. Indeed, several types of viral infections carry cardiovascular risks. Understanding shared and unique mechanisms by which each virus compromises heart function is critical to inform on therapeutic interventions. This review describes how the key viruses known to lead to cardiac dysfunction operate. Both direct host-damaging mechanisms and indirect actions on the immune systems are discussed. As viral myocarditis is a key pathologic driver of heart failure in infected individuals, this review also highlights the role of cytokine storms and inflammation in virus-induced cardiomyopathy.

Purpose of Review: Post-transcriptional modifications are key regulators of gene expression that allow the cell to respond to environmental stimuli. The most abundant internal mRNA modification is N6-methyladenosine (m 6 A), which has been shown to be involved in the regulation of RNA splicing, localization, translation, and decay. It has also been implicated in a wide range of diseases, and here we review recent evidence of m 6 A's involvement in cardiac pathologies and processes.Recent Findings: Studies have primarily relied on gain and loss of function models for the enzymes responsible for adding and removing the m 6 A modification. Results have revealed a multifaceted role for m 6 A in the heart's response to myocardial infarction, pressure overload, and ischemia/reperfusion injuries. Genome-wide analyses of mRNAs that are differentially methylated during cardiac stress have highlighted the importance of m 6 A in regulating the translation of specific categories of transcripts implicated in pathways such as calcium handling, cell growth, autophagy, and adrenergic signaling in cardiomyocytes.Summary: Regulation of gene expression by m 6 A is critical for cardiomyocyte homeostasis and stress responses, suggesting a key role for this modification in cardiac pathophysiology.

Inflammation has recently gained tremendous attention as a key contributor in several chronic diseases. While physiological inflammation is essential to counter a wide variety of damaging stimuli and to improve wound healing, dysregulated inflammation such as in the myocardium and vasculature can promote cardiovascular diseases. Given the high severity, prevalence, and economic burden of these diseases, understanding the factors involved in the regulation of physiological inflammation is essential. Like other complex biological phenomena, RNA-based processes are emerging as major regulators of inflammatory responses. Among such processes are cis-regulatory elements in the mRNA of inflammatory genes, noncoding RNAs directing the production or localization of inflammatory cytokines/chemokines, or pathogenic RNA driving inflammatory responses. In this review, we describe several specific RNA-based molecular mechanisms by which physiological inflammation pertaining to cardiovascular diseases is regulated. These include the role of AU-rich element-containing mRNAs, long non-coding RNAs, microRNAs, and viral RNAs.

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