MICRORNAS IN HYPERTENSION: MOLECULAR MECHANISMS AND THERAPEUTIC PERSPECTIVES - A BIOINFORMATICS APPROACH

This study presents a comprehensive structural bioinformatics analysis of five key microRNAs (miR-21, miR-126, miR-133a, miR-155, and miR-181a), focusing on their secondary and tertiary structure characteristics. Hypertension represents a complex cardiovascular disorder with significant microRNA (miRNA) involvement in its pathogenesis. This study employs an integrated bioinformatics approach to characterize the structural and functional properties of five key miRNAs (miR-21, miR-126, miR-133a, miR-155, and miR-181a) implicated in hypertensive pathophysiology. Through systematic sequence analysis, secondary structure prediction (RNAfold), and tertiary modeling (RNAComposer), we reveal distinct molecular architectures that correlate with their regulatory roles. miR-21 and miR-155 exhibit highly conserved seed regions (85-92% identity) with stable stem-loop configurations, while endothelial-protective miR-126 and miR-133a demonstrate complementary structural features (?G = -32.1 kcal/mol) that may underlie their cooperative function in vascular homeostasis. Network analysis identifies miR-21 as the central hub (betweenness centrality = 0.31) connecting inflammatory (miR-155, miR-181a) and vascular-protective (miR-126, miR-133a) subnetworks. Molecular dynamics simulations reveal heterodimer formation between miR-21 and miR-155 (RMSD = 1.8 A ), suggesting previously unrecognized physical interactions in vascular remodeling. The miR-155/miR-181a module displays compensatory regulation (cross-regulation coefficient = 0.82), explaining clinical observations of treatment resistance. Structural analysis uncovers shared binding motifs (7-mer 5-CAGUGCU-3) that create a competitive binding landscape, potentially accounting for inter-individual variability in therapeutic response. These findings provide a systems-level understanding of miRNA networks in hypertension, offering new avenues for multi-target therapeutic strategies and personalized medicine approaches.