Arterial wall-determined risk factors to vascular diseases

Many decades of research have led to considerable in-depth understanding of circulating factors that may lead to coronary atherosclerosis. However, not every individual with serious known risk factors such as hypercholesterolemia or cigarette smoking develops atherosclerosis. Differential susceptibility of the arterial wall to circulating atherogenic risk factors, which may be largely controlled by genetic variants, may provide this missing link. Endothelial cells, the lining of the arterial wall, are responsible for the integrity and responses to the circulating environment. Dysfunctional endothelial cells and the subsequent proliferation of vascular smooth muscle cells are the prelude of atherosclerosis and acute coronary syndrome. Yet, there have been no detailed studies exploring the interaction between circulating environmental and arterial wall endogenous risk factors in living human subjects. This deficiency is largely the result of restricted access. Genetic factors almost certainly play a key role in directing how the arterial wall responds to circulating “environmental” factors. This endogenous-exogenous (i.e. the arterial wall-circulating) blood balance is the reflection of nature-nurture or gene-environment interaction. Understanding the interaction fully will require direct access to the arteries, and nonhuman primates can provide an excellent model for such investigations. In the current review, we discuss the importance of arterial wall factors in vascular diseases and present a baboon model for practical studies of arterial wall factors and their interaction with circulating factors. Direct biopsy access to baboon arteries will provide a unique opportunity to explore arterial wall susceptibilities and to evaluate the direct effects of diet or pharmaceutical agents on vascular diseases. The use of baboons from large pedigreed families in these studies will enable the identification of genes that interact with these environmental factors in determining individual risk of atherosclerosis.