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The pharmaco-epigenetics of hypertension: a focus on microRNA
Serge Yaacoub1, Ammar Boudaka2, Ali AlKhatib3
1Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Insights
MicroRNAs (miRNAs) play a crucial role in hypertension development and treatment. This review explores how these molecules influence the effectiveness of common hypertension medications through epigenetic mechanisms.
Area of Science:
- Cardiovascular Science
- Molecular Biology
- Pharmacology
Background:
- Hypertension is a leading cause of cardiovascular morbidity and mortality, affecting 1.5 billion people by 2025.
- Its pathophysiology is complex, involving factors like nitric oxide dysregulation and reactive oxygen species.
- Emerging evidence highlights the role of epigenetics, including microRNAs (miRNAs), in hypertension.
Purpose of the Study:
- To review experimentally determined associations between microRNAs (miRNAs) and hypertension pharmacotherapy.
- To highlight the epigenetic mechanisms underlying responses to antihypertensive drugs.
- To elucidate the role of miRNA in the pharmaco-epigenetics of hypertension.
Main Methods:
- Critical review of existing literature.
- Analysis of experimental studies on miRNA and hypertension.
- Focus on epigenetic mechanisms and drug responses.
Main Results:
- MicroRNAs are implicated in the pathophysiology of hypertension.
- Epigenetic modifications, including those involving miRNAs, influence drug efficacy.
- Specific drugs like candesartan, clopidogrel, aspirin, and statins interact with these pathways.
Conclusions:
- MicroRNAs are key players in hypertension pharmacotherapy and pharmaco-epigenetics.
- Understanding miRNA-mediated epigenetic regulation is crucial for optimizing hypertension treatment.
- Further research into miRNA-drug interactions can lead to more effective therapeutic strategies.
Abstract:
Hypertension is a major harbinger of cardiovascular morbidity and mortality. It predisposes to higher rates of myocardial infarction, chronic kidney failure, stroke, and heart failure than most other risk factors. By 2025, the prevalence of hypertension is projected to reach 1.5 billion people. The pathophysiology of this disease is multifaceted, as it involves nitric oxide and endothelin dysregulation, reactive oxygen species, vascular smooth muscle proliferation, and vessel wall calcification, among others. With the advent of new biomolecular techniques, various studies have elucidated a gaping hole in the etiology and mechanisms of hypertension. Indeed, epigenetics, DNA methylation, histone modification, and microRNA-mediated translational silencing appear to play crucial roles in altering the molecular phenotype into a hypertensive profile. Here, we critically review the experimentally determined associations between microRNA (miRNA) molecules and hypertension pharmacotherapy. Particular attention is given to the epigenetic mechanisms underlying the physiological responses to antihypertensive drugs like candesartan, and other relevant drugs like clopidogrel, aspirin, and statins among others. Furthermore, how miRNA affects the pharmaco-epigenetics of hypertension is especially highlighted.
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