Abstract
It is well described process that accumulation of arterial lipids, especially cholesteryl ester (CE), occurs during aging and atherogenesis. In addition, it has been reported that the activity of CE hydrolase (CEH) in aorta is lower in species susceptible to atherosclerosis (rabbit, swine etc.) than in the resistant (rat etc.). Accordingly, the arterial enzymes relating to lipid hydrolysis and synthesis are postulated to play important roles in atherogenesis.
The present investigation was undertaken to clarify the mechanism underlying the accumulation of lipids in arteries during aging and atherogenesis using SHRSP, SHR and WKR which were maintained on lab. chaw for 1, 6 and 11 months after weaning. For this purpose, the following observations were made 1) the change in the level of arterial lipids, 2) the change in the arterial lipid hydrolase activities [CEH, triacylglycerol hydrolase (TGH) and lipoprotein lipase (LPL)] and 3) the change in the membrane stability of lysosomes containing CEH and TGH.
The difference in blood pressure between SHRSP and SHR or SHR and WKR was approx. 20mmHg at 1 month, and approx. 50mmHg at 6 and 11 month, in the increasing order of SHRSP, SHR and WKR. The aortic cholesterol level progressively increased during aging. The degree of the increase was the greatest in SHRSP. The level paralleled with blood pressure. Lysosomal CEH and TGH activities greatly decreased during aging. The activities at 1 month after weaning were SHRSP>SHR>WKR. On the other hand, non lysosomal LPL activity was unchanged during aging. Since lysosomal membrane is known to be sensitive to aging, the stability of liver lysosomal particles was measured by the leakage of CEH and acid phosphatase. The stability of lysosome significantly decreased due to aging in all strains, and the pattern of the decrease in the stability resembled that of the loss of aortic CEH activity.
These results suggest that the accumulation of arterial lipids during aging and atherogenesis results at least partly from the decrease in activity of lysosomal lipolytic enzymes as a consequence of labilization of the lysosomal membrane.
