Effects of Aging on Experimental Atherosclerosis in Nonhuman Primates

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We had quarterly measured over two year period: blood pressure via arm cuff, body weight, rectal temperature, and morphometric measurements including waist and hip circumferences, and blood pressure. Following collection of baseline data, 16 monkeys had been assigned to an atherogenic diet and 7 monkeys to a control diet. We have obtained measures of vascular stiffness: Doppler pulse wave velocity and applanation tonometry; morphologic characterization of atherosclerosis: CE-MRI; and blood chemistry measures: Glucose, cholesterol, triglycerides, HDL, LDL, ox-LDL, CRP, MMPs, TIMPs, MTMMPs, MCP-1, TGF-beta1. After sacrifice, we harvested arterial tissue, including aorta: ascending and descending thoracic, aorta arches; carotid arteries: right and left; coronary arteries: left descending coronary, right coronary. These tissues will be analyzed in the levels of transcription, translation, distribution for the previously mentioned biomolecules. In addition, we have isolated arterial endothelial and smooth muscle cells from these monkeys for in vitro studies. Results shows that pulse wave velocity (PWV) determined by ultrasound examination, and the intimal and medial thickness (IMT) determined by MRI, dynamically increased in monkeys with advancing age and high cholesterol diets. Histochemical observation and morphological analysis indicate that age increases intimal thickness and medial thickness along with atherosclerotic lesions in these domestic monkeys fed normal diets. Interestingly, age effects fat deposition within arterial walls in these domestic monkeys with high cholesterol diets. We will further define the molecular and cellular mechanisms of atherogenesis during aging via combinational analysis of parameters from blood biochemistryl, echo, MRI, histopathological, and gene and protein expression of the aforementioned molecules.