Regulatory Roles of Long Non-Coding RNAs in Arterial Stiffness and Hypertension: Insights from Two African American Studies.

Abstract

Arterial stiffness, commonly assessed via pulse wave velocity (PWV), is marked by reduced arterial elasticity and serves as a significant risk factor for cardiovascular disease and an early indicator of hypertension. This study investigated the regulatory roles of long non-coding RNAs (lncRNAs) in modulating mRNAs associated with arterial stiffness and hypertension, with a particular focus on African Americans, a population disproportionately impacted by hypertension. We utilized whole-blood transcriptome sequencing data from two African American (AA) cohorts with high hypertension prevalence: the GENE-FORECAST study (436 subjects) and the MH-GRID study (179 subjects). Our objectives were to: (1) identify lncRNAs and mRNAs differentially expressed (DE) between the upper and lower tertiles of PWV, (2) determine DE lncRNAs associated with the expression levels of each DE mRNA, and (3) link the lncRNA-modulated mRNAs to hypertension across both datasets. Differential expression analysis revealed 1,035 DE mRNAs and 31 DE lncRNAs between upper and lower PWV groups. Then lncRNA-mRNA pairs significantly associated were identified, involving 31 unique lncRNAs and 1,034 unique mRNAs. Finally, 22 of the lncRNA-modulated mRNAs initially linked to PWV were found associated with hypertension, in both datasets. Interestingly, 30 lncRNAs were linked to the expression of UCP2 (Uncoupling Protein 2), a gene implicated in oxidative stress and endothelial function. Our findings underscore the significant roles of lncRNAs in regulating gene expression associated with arterial stiffness and hypertension. The differential expression of UCP2 in relation to PWV and hypertension, along with its potential regulation by lncRNAs, offers valuable insights into the molecular mechanisms underlying arterial stiffness and its connection with hypertension.