Pathogenic and clinical significance of inflammation-associated MicroRNAs in cardiovascular diseases

Cardiovascular diseases (CVDs) include a spectrum of heart and blood vessel disorders e.g., atherosclerosis, hypertension, coronary artery disease, and peripheral artery disease, leading to global mortality. It is an established fact that inflammation significantly contributes to the pathogenesis of CVDs, acting as a risk factor and accelerating disease progression. miRNAs play a key role in this process. However, studying miRNAs in inflammation presents multiple challenges, including the regulation of multiple target genes by a single miRNA and the involvement of the same inflammatory miRNA in more than one type of CVD. In this review, we explored the role of miRNAs in regulating inflammation in different types of CVDs, including hypertension, coronary artery disease, and peripheral artery disease, along with their common target genes. These miRNAs serve as key regulators of inflammatory pathways by modulating cytokine production, immune cell recruitment, and endothelial cell function, thereby playing dual roles in promoting or mitigating inflammation. Several miRNAs play a pivotal role in inflammation, contributing to various CVDs. miR-155A and miR-146a regulate inflammatory pathways by targeting TNF-α, NF-κB, and IRAK1/TRAF6, linking them to atherosclerosis, myocardial infarction (MI), and acute coronary syndromes (ACS). miR-21 modulates TGF-βR1, PDCD4, and SMAD7, promoting fibrosis and vascular remodeling, which are associated with hypertension and heart failure. miR-221/222 influences vascular smooth muscle cell (VSMC) proliferation by targeting p27(Kip1) and JNK1/ETS-1, leading to neointimal hyperplasia and hypertension. Additionally, miR-133a/b regulates Notch signaling, contributing to atherosclerosis and cardiac fibrosis. These miRNAs serve as potential biomarkers and therapeutic targets for inflammation-driven CVDs.