O70 INVOLVEMENT OF MICRORNAs-146a-5P, -155-5P, AND -29b-5P IN CARDIAC REMODELLING AND DYSFUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Background: MicroRNAs have been implicated in the pathogenesis of cardiovascular disease. However, the contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology. Aim: We investigated the role of miR-146a-5p, -155-5p, and -29b-5p in the development of cardiac hypertrophy and dysfunction in male and female spontaneously hypertensive rats (SHR). Methods: Seven (7)-month-old SHR (n=7 male, n=10 female), and age- and sex-matched normotensive Wistar Kyoto rats (WKY, n=7 male, n=9 female) were used for the study. Cardiac geometry and function were determined from echocardiography. Plasma levels of inflammatory markers were measured by ELISA. Collagen fraction area was determined from histological sections of the left ventricle (LV). MicroRNA, and mRNA expression of target genes was determined in the LV by RT-qPCR. Group differences were ascertained from 2-way ANOVA. Associations were determined from pearson's correlation. Results: In SHR, normalised heart and LV masses, LVPWTd, RWT, E, A, E/e’, and collagen fraction area were significantly greater compared to WKY. MidFS, e’, and a’ were significantly lower in SHR versus WKY. Female rats exhibited significantly greater LV mRNA expression of Lox1, Col1a/Col3a ratio, and plasma levels of CRP, IL-6, and TNF-α compared to males. MiR-29b-5p showed similar expression levels across experimental groups. MiR-146a-5p was upregulated in SHR and exhibited positive associations with BP, normalised heart and LV masses, RWT, collagen fraction area, and E/e’ ratio, but negative associations with e’. Conversely, miR-155-5p was downregulated in females and only positively associated with absolute heart, LV, kidney masses, and stroke volume. Conclusion: Upregulation of miR-146a-5p was associated with indices of concentric LVH, diastolic dysfunction, reactive fibrosis, and may be involved in the hypertensive-induced LV remodelling; whereas, changes in expression of miR-155-5p may be involved with a cardiac phenotype related to sexual dimorphism.