Dual ARB/NEP Inhibition with LCZ696 improved endothelial regeneration in an experimental model of metabolic syndrome

Abstract

To demonstrate that LZC696 (L) reduces organ damage in an experimental model of metabolic syndrome, were explored two mechanisms: anti-inflammatory effects through the IL-6Ralpha pathway and through MAS1R, the production of endothelial repair mediated by VEGFR2+/CD133+ endothelial progenitor cells (EPCs). Experimental model of metabolic syndrome was realized by WKY rats and SHRs. SHR and WKY received a fructose diet in drinking water at 10% v/v for 12 weeks (FFHR and FFR receptivity). Chronic treatment with L: (68 mg / kg per day for 6 weeks) and valsartan (V) (34 mg / kg per day for 6 weeks, as control equimolar group. Was determined: SBP, fast glycaemia and TTGO, left ventricular hypertrophy (HVI), vascular remodelling, hsCPR expression, and vascular expression in mesenteric tissue of IL-6Ralfa, STAT3, VEGFR2 and CD133 were determined. The experimental model was confirmed. L treatment reverted SBP, HVI, remodelling and vascular inflammation, decreased STAT3 expression and hsCPR in FFHR. Additionally, the most important finding was that L produced an increase in the expression of resident EPCs in the endothelial tissue of mesenteric tissue.