Involvement of microRNA-146a-5p, but not -155-5p and -29b-5p, in left ventricular remodeling and dysfunction in spontaneously hypertensive rats

Background: The contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology. Aim: The role of miR-146a-5p, miR-155-5p, and miR-29b-5p in cardiac hypertrophy and dysfunction was investigated in spontaneously hypertensive rats (SHR). Methods: Seven-month-old SHR (n=7 male, n=9 female), and normotensive Wistar Kyoto rats (WKY; n=7 male, n=9 female) underwent echocardiography. Plasma concentrations of inflammatory markers were measured by ELISA. Interstitial and perivascular fibrosis and percentage macrophage infiltration were determined by histology. LV mRNA expressions of cardiac remodelling markers and miRNA expressions were determined by RT-PCR. Results: Circulating VCAM-1, macrophages infiltration, interstitial and perivascular fibrosis, RWT, E/e', and LV mRNA expression of NFKBIA and SOD2 were greater in SHR. MidFS, e' and a' were lower in SHR. Expression of LOX1, Col1a/Col3a ratio, circulating CRP, IL-6, and TNF-α, and RWT were greater in females. No difference in miR-29b-5p expression was noted. MiR-155-5p expression was lower in female and associated with stroke volume and absolute heart and LV masses. MiR-146a-5p expression was greater in SHR and associated with SBP, circulating VCAM-1, macrophage infiltration, interstitial fibrosis, normalised heart and LV masses, RWT and a'. MiR-146a-5p was also associated with circulating VCAM-1 after adjustments for SBP. In addition, greater expression of miRNA-146a-5p reversed the relationship between circulating VCAM-1 and macrophage infiltration. Conclusion: Changes in expression of miR-155-5p may be involved with a cardiac phenotype related to sexual dimorphism. Conversely, upregulation of miR-146a-5p expression may act as a counter-mechanism induced by myocardial inflammation in the setting of reactive fibrosis, established LV hypertrophy and impaired diastolic function.