MicroRNA-24-3p targeting Top1 in perirenal fat is involved in circulating inflammation and high cardiovascular disease risk in patients with primary aldosteronism.

Abstract

Context: Patients with primary aldosteronism (PA) are at a high risk of cardiovascular diseases (CVD) and metabolic syndrome. Notable inflammatory and fibrotic changes and differential microRNA (miRNA) expression profiles in the perirenal fat observed in PA may contribute to this increased risk, however, which has not been fully elucidated.

Objective: This study aimed to explore the role of high expression of miR-24-3p in perirenal fat in circulating inflammation and its correlation with a high risk of CVD in patients with PA.

Methods: Perirenal fat thickness (PRFT) measured by computed tomography (CT), miR-24-3p expression in perirenal fat, circulating inflammatory factors from adrenal veins and peripheral blood in patients with PA were analyzed. In vitro, white and brown adipocytes with miR-24-3p overexpression or inhibition respectively were stimulated with aldosterone and a unidirectional co-culture model of adipocytes and HUVEC was established. The target genes of miR-24-3p were identified.

Results: Patients with PA and CVD have significantly higher PRFT than those without CVD. The expression level of miR-24-3p in perirenal fat was significantly positively correlated with PRFT. MiR-24-3p was significantly upregulated in the perirenal fat of PA and was associated with increased adipogenesis, inflammation, and oxidative stress, correlating with plasma aldosterone concentration (PAC), PRFT, cardiac remodeling, and weight gain. The IL-6 level in the peripheral blood was elevated in patients with PA and CVD, and the affected adrenal vein had the highest IL-6 level. Targeting Top1, miR-24-3p modulated aldosterone-induced effects in adipocytes and influenced IL-6 secretion, thereby affecting HUVEC.

Conclusion: The upregulation of miR-24-3p in the perirenal fat induced inflammation and oxidative stress by targeting Top1, which may contribute to a high risk of CVD in patients with PA.