Sexual dimorphism in the long-term impact of postnatal nutritional programming on cardiac sensitivity to ischemia-reperfusion injury in vivo

Abstract

Nutritional disturbances during the postnatal period may be responsible for a predisposition in adulthood to increased cardio-metabolic risk and a greater myocardial vulnerability to ischemia. However, these data have mainly been obtained in male mice, but less is known for females. The aim of our study was to evaluate the impact of postnatal overfeeding on cardiac sensitivity after in vivo ischemia-reperfusion (I-R) on both sexes. PNOF was induced by reduction of litter size of C57/BL6 mice immediately after birth: normally-fed group (NF) litters were composed of 9 pups/mother and overfed group litters (OF) of 3 pups/mother. The in vivo ischemia was induced by a 45 min ligation of the left anterior interventricular artery, followed by 24 hours of reperfusion, in hearts from 4 and 6 months aged male and female mice. The area at risk (AAR) was determined by Evans blue coloration and the infarct size by TTC staining. PNOF induced an early and permanent increase in body weight in OF group, for males (4 months: +13%; 6 months: +23%) and female mice (4 months: +23%; 6 months: +27%). A significant increase of infarct size was observed in hearts of overfed male mice aged of 4 and 6 months (respectively +37% and +32% of AAR), but it was just a trend for female mice at the same age. However, postoperative mortality was higher in both female groups (NF and OF) at 4 months (44%) and 6 months (37%) of age, as compared to males (4 months: 29%; 6 months: 18%). Nutritional programming through short-term PNOF induced a higher susceptibility to myocardial I-R injury in vivo, however with different intensities according to sex in mice. The mechanism of this different sexual dimorphism in our model is not well understood, but it could involve distinct levels of cardioprotective pathways expression.