Accelerated rates of collagen synthesis in atherosclerotic arteries quantified in vivo.

Abstract

Rates of arterial collagen and noncollagen protein synthesis were quantified in vivo in rabbits maintained for 4 months on a control diet or the same diet supplemented with 2% peanut oil and 0.25% cholesterol. Thoracic aortas from animals fed the atherogenic diet exhibited raised lesions covering 75% to 100% of the surface. The dry delipidated weight and collagen content of these arterial segments both were significantly increased. The rates of protein synthesis were determined in rabbits given a bolus intravenous injection of 3H-L-proline (1.0 mCi/kg) and unlabelled proline (7 mmol/kg) to attain steady-state levels of specific radioactivity of free proline in plasma and tissues. Plasma proline specific activity decreased only 20% over a 5-hour period and was similar to free proline in arterial tissue, skin, and lung. Collagen synthesis rates (ng/mg dry delipidated weight per hour) were increased 10-fold in the intima plus inner media of atherosclerotic thoracic aortas compared with controls. Rates of collagen synthesis were also increased in the abdominal aortas, whereas protein synthesis in lung and skin was unaffected by diet. Increased rates of collagen synthesis in atherosclerotic arteries significantly exceeded the increases in noncollagen protein synthesis. In addition, collagen synthesis rates in vivo were 12 to 20 times greater than previously measured in vitro. These results demonstrate for the first time in vivo that collagen accumulation in the developing atherosclerotic plaque is in part due to accelerated rates of collagen synthesis by intimal smooth muscle cells.