Statin Treatment in Hypercholesterolemic Pregnant Mice Reduces Cardiovascular Risk Factors in Their Offspring

Abstract

Increasing evidence suggests that hypercholesterolemia during pregnancy initiates pathogenic events in the fetus leading to increased risk of cardiovascular disease in the adult offspring. In this study we examined in mice whether pharmacological intervention using statins in late pregnancy could alleviate the detrimental effects of a high-fat, high-cholesterol (45% fat) maternal diet on the health of the dams and their offspring. Pregnant C57 mice on high-fat, high-cholesterol diet were given the 3hydroxy3methylglutaryl-coenzyme A reductase inhibitor pravastatin in the drinking water (5 mg/kg of body weight per day) in the second half of pregnancy and during lactation to lower cholesterol and improve postweaning maternal blood pressure. Weaned offspring were then fed the high-fat, high-cholesterol diet until adulthood (generating dam/offspring dietary groups high-fat, high-cholesterol/high-fat, high-cholesterol and high-fat, high-cholesterol plus pravastatin during the second half of pregnancy and lactation/high-fat, high-cholesterol). These groups were compared with offspring from mothers fed standard chow (control), which were then fed control diet to adulthood (control/control). Compared with high-fat, high-cholesterol, high-fat, high-cholesterol plus pravastatin during second half of pregnancy and lactation dams showed significantly reduced total cholesterol concentrations and reduced systolic blood pressure. The high-fat, high-cholesterol plus pravastatin during second half of pregnancy and lactation/high-fat, high-cholesterol offspring were significantly lighter, less hypertensive, and more active compared with the high-fat, high-cholesterol/high-fat, high-cholesterol group. Total serum and low-density lipoprotein cholesterol concentrations were significantly lower, and high-density lipoprotein cholesterol concentrations were raised in high-fat, high-cholesterol plus pravastatin during the second half of pregnancy and lactation/high-fat, high-cholesterol offspring, compared with the high-fat, high-cholesterol/high-fat, high-cholesterol group. The control/control offspring showed the lowest blood pressure and cholesterol levels. These findings indicate that the cholesterol-lowering effect of statins in pregnant dams consuming a high-fat, high-cholesterol diet leads to reduced cardiovascular risk factors in offspring that are sustained into adulthood.