Increased arterial collagen synthesis in experimental canine atherosclerosis

Abstract

The rates of collagen synthesis by normal and atherosclerotic canine arteries have been measured in vitro by determining the amount of peptidyl [ 14C]hydroxy-proline formed after incubation at 38° for 1–4 hr in the presence of [U- 14C] l-proline. Atherosclerotic lesions were produced by feeding dogs a cholesterol supplemented essential fatty acid deficient, semi-synthetic diet for 14 months. Atherosclerotic regions of the aorta, coronary, renal, mesenteric, iliac and femoral arteries were found to synthesize collagen at a rate between 5 and 20 times that of non-atherosclerotic regions of the same arteries, or that of normal arteries from dogs fed a stock laboratory ration. The degree of stimulation of collagen synthesis was related to the extent of the atherosclerotic process in the artery, the mean rates of synthesis in femoral arteries being 97 ± 42 ng/g/4 hr when no atherosclerosis was present, 476 ± 397 in arteries with between 40% and 80% atherosclerosis and 1954 ± 821 in arteries with 100% surface involvement. The percentage of protein synthesis represented by collagen rose from a mean of less than 5% in normal aortic branch arteries to 14% in severely atherosclerotic branch arteries, showing that the increases in collagen synthesis were not associated simply with an overall increase in protein synthesis. Segments of atherosclerotic and normal arteries were also incubated with [5- 3H] l-proline and autoradiographs prepared following the incubation. These autoradiographs provided evidence suggesting that the thickened intima was more responsible for the observed increases in synthesis than the media and that these increases were brought about by enhanced rates of collagen formation within each cell.