Hypercholesterolemia superimposed by experimental hypertension induces differential distribution of collagen and...

We studied the mural distribution of collagen types I and III and tropoelastin in enhanced experimental atherogenesis induced in rabbits by hyperlipidemia superimposed by hypertension. Animals were fed a high-cholesterol diet for 5 weeks and also subjected to midthoracic aortic coarctation for 4 weeks. Serum cholesterol levels were increased and blood pressure was elevated proximal to the coarctation. Foam cell lesions developed in the aorta proximal to the coarctation. In situ hybridization and immunohistochemistry showed that gene expression of collagen types I and III and tropoelastin was upregulated, with a differential distribution across the arterial wall. New collagen type I was mainly distributed in the intima, the outer media, and the adventitia. New collagen type III was spread more uniformly across the wall, including the adventitia, whereas tropoelastin was mainly localized in intimal foam cell lesions. Morphometric data showed an increase in wall thickness. These results suggest that collagen types I and III play a role in remodeling of the aortic wall in response to hypertension. The remarkable involvement of the adventitia in this response indicates that the adventitia is an important component of the arterial wall. Tropoelastin is closely associated with foam cell lesion formation, suggesting a role for this component in atherogenesis as well.