Pharmacoepigenomic Impact of Antihypertensive Drugs on miRNome and Proteome and Its Potential Influence on Health and Side Effects

Antihypertensive drugs are widely used for the treatment of hypertension, and the choice of drug and dosage is based on trial and error. The variability in drug response and adverse reactions leads to the poor adherence to treatment. Epigenetic modulation is one of the major mechanisms that may contribute to the variability in drug responses, and microRNAs (miRNAs) can serve as crucial epigenetic regulators and have also been reported to be associated with hypertension pathogenesis. The objective of this study is to investigate the regulatory effects of commonly used antihypertensive drugs on the endothelial miRNome in human aortic endothelial cells. We aim to integrate miRNA expression data with proteomic analyses to elucidate drug-induced molecular mechanisms relevant to hypertension treatment. Whole genome small RNA sequencing was performed, followed by whole proteome analysis using LC-MS/MS comparing between control and treated samples. The treatments induced significant differential regulation of several miRNAs and proteins; among these, a few reflected reverse relationships with miRNA regulation and protein expression. Certain miRNAs and their corresponding target proteins seem to distinguish between good therapeutic outcomes and potential side effects. This study unravels the potential role of drug-induced miRNAs in inducing post-transcriptional modifications to cause the differential expression of certain proteins that may induce not only therapeutic effects or drug side effects but can also indicate the potential for drug-repurposing in other diseases.