Atherosclerotic cardiovascular disease is responsible for over 19 million deaths annually worldwide and coronary artery disease remains the leading cause of death among cardiovascular diseases. It is well established that maternal health behaviors during pregnancy impact offspring's atherosclerotic disease burden later in life. Limited data exists describing the impact of maternal exercise during pregnancy on the atherosclerotic disease burden of offspring throughout life. Therefore, the specific aims of this proposal are to: 1) determine whether vascular function differs between offspring from exercise trained and sedentary swine 2) determine whether atherosclerotic disease differs between offspring from exercise trained and sedentary swine and 3)determine whether behaviors linked to atherosclerosis (physical activity and food consumption) differ between offspring from exercise trained and sedentary gilts. These aims will be addressed using a well established swine model of exercise training. The swine is similar to humans in maximal oxygen consumption, coronary artery anatomy, systemic hemodynamics (mean arterial pressure, heart rate, and cardiac output), and development of atherosclerosis when fed a high fat diet. Animals will be randomly assigned to one of three experimental groups (sedentary, exercise trained, exercise trained + caloric supplementation). Exercise will be initiated 1 week following artificial insemination and will continue for the 15 week gestational period. Exercise training will consist of treadmill exercise for 30-45 minutes a day, five days a week, at an intensity of 65-85% of maximal heart rate. Offspring will be fed a high fat diet following weaning to initiate the atherosclerotic disease process. The left anterior descending coronary artery and femoral artery of offspring will be used for measurements of endothelial function, nitric oxide bioavailability, vascular smooth muscle function, and histological measurements of atherosclerosis at three distinct time points throughout life (48 hours, 6 months, 12 months following birth). Vascular function experiments will utilize an in vitro wire myograph technique and measurements of atherosclerosis will be performed using Sudan IV, Verhoeff VanGiesson, and Hematoxylin/Eosin staining. The findings of this proposed investigation could provide evidence supporting a role for maternal exercise during pregnancy in the primary prevention of atherosclerotic disease development.
|Program type||Scientist Development Grant|
|Effective start/end date||01/01/2012 → 12/31/2015|