Сanonical WNT signaling and myocardial remodeling in arterial hypertension and chronic kidney dysfunction

INTRODUCTION. Beta-catenin is a structural protein of adhering junction and intercalated discs of cardiomyocytes as well as the main intracellular messenger of the canonical WNT (cWNT) signaling pathway. The dysregulation of the cWNT signaling and the rearrangement of the cardiomyocyte cytoskeleton accompany the cardiovascular disorders in chronic kidney disease (CKD). THE AIM: to investigate the expression and distribution of β-catenin, calcineurin A, and TGF-β1 in the myocardium of spontaneously hypertensive rats (SHR) with CKD, sham operated SHR and Wistar Kyoto rats of the corresponding age. MATERIAL AND METHODS. Systolic blood pressure (BP), heart rate (HR), myocardial mass index (MMI), creatinine concentration (Cr), myocardial beta-catenin expression and renal Klotho expression, morphological light-optical study of kidney and myocardium tissues was performed in sham operated (SO) Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and SHR with 5/6 nephrectomy (Nx). RESULTS. SHR rats showed higher values of BP, MMI, cardiomyocyte diameter, myocardial fibrosis area, and lower Klotho levels compared to WKY rats. Nx SHR had lower kidney function and renal Klotho expression, higher BP and MMI compared to SHR. An increase in the cardiomyocytes diameter and the area of myocardial fibrosis was accompanied by the overexpression of β-catenin, calcineurin A, and TGF-β1 in the myocardium. CONCLUSION. The upregulation of canonical Wnt signaling and cellular programs of cardiomyocyte hypertrophy mediated by Klotho deficiency can be involved in myocardial remodeling in chronic renal dysfunction.

cardiac hypertrophy, chronic kidney disease, arterial hypertension, beta-catenin, Klotho, canonical WNT signaling pathway

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