PS-B03-9: EPLERENONE PREVENTS CARDIAC FIBROSIS BY INHIBITING ANGIOGENESIS IN UNILATERAL URINARY OBSTRUCTION RATS

Abstract

Objective: Cardiovascular disease constitutes the leading cause of mortality in patients with chronic kidney disease (CKD), which is termed cardiorenal syndrome type 4 (CRS-4). The aim of our experiments was to clarify the relationship between angiogenesis and endothelial-mesenchymal transition (End-MT) and the the development of pathological cardiac remodeling and fibrosis in unilateral urinary obstruction (UUO) rats. Also, our study was to confirm eplerenone prevents cardiac fibrosis by inhibiting angiogenesis in unilateral urinary obstruction rats. Design and method: We used a 180-day rat model of unilateral ureteral obstruction (UUO) to replicate the CRS model. Using eplerenone, a blocker of mineralocorticoid receptor (MR), to test the effect of aldosterone in cardiac fibrosis induced by UUO. HE staining was performed to observe the pathology of myocardial tissue. The degree of myo-cardial tissue fibrosis was observed by Masson and Sirius red staining. Immunohistochemical staining was applied to detect the expression of CD34 and CD105 in myocardial tissue, and immunofluorescent staining was performed to examine the expression of CD34, COLI/COLIII and alpha-SMA. The expression of signal pathway-related protein VEGFA, VEGFR2, nuclear factor kappa-B and IL-1 beta were tested by western blot. RT-PCR was used to detect the mRNA levels of SGK-1, nuclear factor kappa-B and IL-1beta. Results: The results shows that the development of pathological cardiac remodeling and cardiac dysfunction in UUO rats. Moreover, there was more angiogenesis and endothelial-mesenchymal transition (End-MT) in the UUO group, and these effects were inhibited by eplerenone. Conclusions: The results indicated that this cardiac fibrosis was associated with angiogenesis and endothelial-mesenchymal transition (End-MT) related to aldosterone and mineralocorticoid receptor (MR) activation. Moreover, in association with the MR/IL-1beta/VEGFA signaling pathway, early treatment with the MR antagonist eplerenone in rats with UUO-induced CKD may significantly attenuate MR activation and cardiac fibrosis.