MO440: Intramyocardial Artery Fibrosis and Media Hypertrophy are Associated With Beta-Catenin and Calcineurin Expression in the Model of Arterial Hypertension and CKD

Abstract

Abstract BACKGROUND AND AIMS Intramyocardial arteries (IA) are one of the components of pathological cardiac remodeling. We have previously shown that cardiomyocytes hypertrophy and interstitial fibrosis are accompanied by calcineurin (CaN) and β-catenin (βCat) up-regulation in the model of arterial hypertension (AH) and chronic kidney disease (AH-CKD). In this pilot study, we investigated whether IA remodeling is associated with CaN and βCat expressions in medial (MC) and adventitial (AC) cells in AH-CKD. METHOD AH-CKD was induced by 5/6 nephrectomy (5/6NE) in spontaneously hypertensive rats (SHR-NE, n = 8). Sham-operated (SO) SHR (SHR-SO, n = 8) and Wistar Kyoto rats (WKY-SO, n = 8) were controls. Systolic blood pressure (SBP), myocardial mass index (MMI), serum creatinine (Cr), FGF23, renal Klotho (rKl), IA wall thickness (WT), perivascular fibrosis (PF), number of AC, βCat-positive AC (βCat + AC) to all AC ratio, CaN and βCat expression in MC were analyzed for 2 months after 5/6NE or SO. RESULTS The cardiac remodeling indexes—SBP, MMI, WT, AC, PF, as well as FGF23, were higher and rKl was lower in SHRs vs WKY-SO and in SHR-NE versus SHR-SO (Table). The increase in WT was accompanied by MC hypertrophy (Figure 1) with cytoplasmic CaN expression (data not shown) and PF with the increase in the number of AC in SHR-SO vs WKY-SO (Table). PF, medial hypertrophy and fibrosis of IA were accompanied by the apparent expression of CaN and βCat in the MC (Figure 1), an increase in the total number of AC and the βCat + AC accumulation in AH-CKD (Table, Figure 2). CONCLUSION IA remodeling in the setting of AH and CKD seems to be associated with СаN and βCat up-regulation in medial and adventitial cells subpopulations. Further study is needed to identify the origin of CaN/βCat expressing cells and the mechanisms of their involvement in the pathology of vascular wall alterations.