Cardiovascular diseases (CVDs), including coronary heart disease, hypertension, and heart failure are a leading cause of morbidity and mortality worldwide. Early detection and diagnosis are important to improve the prognosis and treatment of CVDs. Growing evidence reveals the important role of epigenetic mechanisms, including DNA methylation, Histone methylation and acetylation, and non-coding/micro RNAs (ncRNA/ miRNAs), in the manifestation of CVDs. More than 30 new methylation sites are associated with Acute Myocardial Infraction (AMI). Also, differential methylations of the genes important in CVDs and the enzymes that incur DNA methylation, DNA methylases, are also reported. Further, epigenetic modification of histones, including methylation and acetylation, play a critical role in atherosclerotic plaque formation. All these serve as important biomarkers to understand and design therapeutic targets for heart diseases.

Nitric Oxide (NO) influences cardiac contractility by its actions on cardiac myocytes. DNA methylations and histone modifications play an important role in its production by endothelial nitric oxide synthetase (eNOS) and purportedly in its downstream signaling. However, data on NO-induced DNA methylation directly in the heart is currently lacking which is needed to provide a critical insight into the actions of this vasodilator. In addition, hypomethylation of Angiotensin Converting Enzyme (ACE) and Angiotensin Type I Receptor (AT1R) genes were found to be key players in hypertension and CVD progression. Also, increasing evidence suggests that the prohypertrophic and profibrotic effects of Angiotensin II (ANG II) and Endothelin-1 (ET-1) are mediated by histone deacetylases (HDACs) in target cells. Consequently, silencing of histone deacetylases are shown to attenuate ANG II-induced proliferation and migration of cardiac fibroblasts. However, HDACs have a consequential role in deacetylation of many non-histone proteins including those important for mitochondrial homeostasis. Other epigenetic modulators of CVDs include ncRNAs and miRNAs.

This research topic aims to address the critical role of epigenetic modifications such as target DNA methylation, histone acetylation/deacetylation, and miRNAs in CVDs. As drugs targeting epigenetic modifiers such as HATs and HDACs offer a viable strategy in the treatment of cardiac hypertrophy, fibrosis and other CVDs, it’s important to study their safety and efficacy. Also, evidence for epigenetic regulation of paracrine signaling involving NO, ANG II, ET-1, and others are mostly derived from non-cardiovascular sources, indicating the need for rigorous studies in cardiovascular tissue to enhance our understanding and to devise new therapeutic targets.

The scope of this research proposal falls within the realm of cardiac pharmacology with emphasis on role of epigenetic modifications in the progression of cardiovascular diseases. Potential contributors are invited to address the following themes:

- Recent advances in understanding the role of epigenetic modifications in the cause and progression of CVDs
- Recent research into potential biomarkers for conditions such as of MI, Ischemic Reperfusion, Vascular calcification etc.
- Mechanisms of DNA methylation/epigenetic modifications in the downstream signaling of nitric oxide.
- Studies involving the potential therapeutic candidates, HDAC inhibitors, and their differential effects on Ang II/Epi I induced cardiac fibrosis and mitochondrial homeostasis.
- Investigations exploring the role of miRNAs in hypertension and cardiac function in general and the effects of drugs targeting miRNAs.
- Understanding Histone acetylation related drugs and their therapeutic effectiveness to target CVDs including vascular calcification
- Advances in research methodologies to study epigenetic modifications
- Reviews summarizing the recent advances in therapeutic drugs for epigenetic modifiers

Suggested formats for the submissions include, Original Research, Mini-Review, Review, Case Report, Perspectives, and Brief Research Report.

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Frontiers in Pharmacology

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