Dual disruption of eNOS and ApoE gene accelerates kidney fibrosis and senescence after injury

The relationship between cellular senescence and fibrosis in the kidney is being elucidated we have identified it as therapeutic target recent studies. Chronic disease has also become a lifestyle disease, often developing on background of hypertension dyslipidemia. In this study, clarify effect interaction these two conditions senescence. Wild type mice (WT), apolipoprotein E-/- (ApoEKO), endothelial nitric oxide synthase (eNOS)-/- ApoE-/- (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed 8–10 week old male degree renal tubular injury, evaluated. DKO manifested elevated blood pressure, higher total cholesterol lower HDL than WT. showed sustained injury molecule-1 protein expression. Kidney significantly ApoEKO DKO. mRNA expression genes related to highest Zinc-?2-Glycoprotein heme oxygenase-1 decreased Furthermore, p53, p21 p16 increased both DKO, with highest. Senescence associated ?-gal positive tubule area Increased DNA damage rapamycin–autophagy spatial coupling compartments (TASCCs) formation found Mice dysfunction dyslipidemia developed accelerated even young after injury. These data highlight fact managing lifestyle-related diseases from age important for CKD prevention.