Abstract 10581: Sexual Dimorphism in Acute Myocardial Infarction-Induced Acute Kidney Injury

Abstract

Introduction: Acute kidney injury (AKI) is a common complication of acute myocardial infarction (AMI) in both males and females, increasing mortality rate substantially. Premenopausal females appear to be more protected, suggesting a potential protective role of estrogen. Hypothesis: We hypothesized that premenopausal female mice are more protected against AMI-induced AKI and that is potentially due to female sex hormones. Materials and Methods: AMI was induced by ligating the left anterior coronary artery in male and premenopausal female mice. Kidney histological, molecular, and functional parameters were assessed after 7 days. Surgical menopause was induced in AMI-female mice to evaluate estrogen-mediation of the observed renal protection. Results: 7days post-AMI enhanced fibrosis and glomerular retraction were observed in AMI-males, only. Both sexes exhibited a comparable marked increase in glomerular reactive oxygen species (ROS) and DNA fragmentation that was associated with a marked decrease in total NAD kidney levels. Increased release of IL-1β, a pro-inflammatory cytokine, and caspase-3, a proapoptotic marker, and α-smooth muscle actin, a profibrotic biomarker, was seen in AMI-male mice, only. NAD + biosynthetic enzymes, including nicotinamide phosphoribosyl transferase and nicotinamide riboside kinase-1, increased only in AMI-females, whereas male counterparts showed a substantial decrease in mitochondrial bioenergetic enzymes such as Sirtuins 1 and 3, along with an increase in Poly [ADP-ribose] polymerase 1, an NAD + consuming enzyme. Exacerbated kidney damage in AMI-females post-ovariectomy was seen with aggravated morphological alterations, increased ROS generation, and enhanced pro-inflammatory cytokine release, and altered NAD + biosynthetic and mitochondrial bioenergetic enzymes. These changes translated into exacerbated kidney function as evidenced by a decrease in creatinine clearance in AMI-male and female mice, while urine output declined in AMI-male mice only. A further decrease in creatinine clearance and urine output was observed in AMI-female mice following ovariectomy. Conclusion: Our findings suggest that AMI induced AKI in both sexes with pre-menopausal female mice being more protected.