A possible mechanism for accelerated atherogenesis in male versus female rats.
Dietary fat and cholesterol enter the circulation as chylomicrons. They are removed from the circulation by attachment to lipoprotein lipase located on the endothelial surfaces. As the result of lipoprotein lipase action, chylomicrons are partially hydrolyzed and then reenter the circulation as remnants, which are rapidly cleared by the liver. We investigated the fate of 3H-retinol- and 14C-cholesterol-labeled chylomicrons injected into male and female rats. The disappearance curves of chylomicrons from the circulation were not significantly different in males and females, which suggests that translocation from plasma to endothelium is similar for both sexes. However, in male rats, the "dwell time" of chylomicrons on the endothelium was significantly prolonged. At 10 and 20 minutes after chylomicron injection, more label was found in the livers of female than male rats. The opposite was true for hearts. Male hearts contained significantly more endothelium-bound chylomicrons when compared with female hearts. This increase in dwell time may allow greater cholesterol deposition in the endothelium of male rats. The more rapid processing of chylomicrons was associated with a 300% greater postheparin lipoprotein lipase in female rats, which suggests a greater enzyme density at chylomicron attachment points on endothelium.
Staprans
I
I
Lipid Research Lab, VA Medical Center, San Francisco, CA 94121.
Felts
J M
JM
D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002784:Cholesterol; D002914:Chylomicrons / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D014316:Tritium; D014801:Vitamin A
D002250:Carbon Radioisotopes; D002914:Chylomicrons; D014316:Tritium; D014801:Vitamin A; D006493:Heparin; D002784:Cholesterol; D008071:Lipoprotein Lipase