Aldosterone is a mineralocorticoid hormone that participates in the regulation of electrolyte balance, blood pressure, and tissue remodeling. Primary aldosteronism (PA) is characterized by excess production of aldosterone from the adrenal glands and is the most common and treatable cause of secondary hypertension. IL-6 trans-activation contributes to aldosterone-induced cardiac fibrosis.

Mice receiving recombinant soluble gp130 and Sgp130 Knockin Transgenic Mice prevented myocardial fibrosis and cardiac hypertrophy by aldosterone infusion. To further investigate the role of IL-6 trans-signaling in aldosterone-induced cardiac fibrosis, we measured the severity of myocardial fibrosis in aldosterone infusion mice models including an IL-6 chemical inhibitor and Sgp130 Knockin Transgenic Mice. In cardiac fibroblasts, IL-6 trans-signaling played a critical role in aldosterone-induced IL-6-enhanced fibrosis-related factor expression.

Intracellular signaling occurred through the mineralocorticoid receptor/PI3K/Akt/NF-kB pathway. Aldosterone significantly induced IL-6 protein and mRNA production in human umbilical vein endothelial cells. In cell studies, we investigated the possible molecular mechanism how aldosterone induced IL-6 secretion and the further effects of collagen production. In addition, plasma IL-6 levels were positively correlated with 24-hour urinary aldosterone and echocardiographic parameters. The PA patients had higher plasma IL-6 levels, left ventricular mass index, degree of myocardial fibrosis, and more impaired diastolic function than the EH patients. In this clinical study, we prospectively enrolled 25 patients with primary aldosteronism (PA) and 26 patients with essential hypertension (EH). We investigated whether aldosterone induces the expression of IL-6 and thereby contributes to the fibrotic process. Interleukin-6 (IL-6) is a key mediator in the fibrotic process, however the effect of aldosterone on the expression of IL-6 remains unclear. An excess of aldosterone results in cardiac remodeling and fibrosis.

Alta dele a miana