Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys.

Abstract

Mechanisms that might be responsible for the low levels of high density lipoprotein (HDL) associated with hypertriglyceridemia were studied in an animal model. Specific monoclonal antibodies were infused into female cynomolgus monkeys to inhibit lipoprotein lipase (LPL), the rate-limiting enzyme for triglyceride catabolism. LPL inhibition produced marked and sustained hypertriglyceridemia, with plasma triglyceride levels of 633-1240 mg/dl. HDL protein and cholesterol and plasma apolipoprotein (apo) Al levels decreased; HDL triglyceride (TG) levels increased. The fractional catabolic rate of homologous monkey HDL apolipoproteins injected into LPL-inhibited animals (n = 7) was more than double that of normal animals (0.094±0.010 vs. 0.037±0.001 pools of HDL protein removed per hour, average±SEM). The fractional catabolic rate of low density lipoprotein apolipoprotein did not differ between the two groups of animals. Using HDL apolipoproteins labeled with tyramine-cellobiose, the tissues responsible for this increased HDL apolipoprotein catabolism were explored. A greater proportion of HDL apolipoprotein degradation occurred in the kidneys of hypertriglyceridemic than normal animals; the proportions in liver were the same in normal and LPL-inhibited monkeys.Hypertriglyceridemia due to LPL deficiency is associated with low levels of circulating HDL cholesterol and apo Al. This is due, in part, to increased fractional catabolism of apo Al. Our studies suggest that variations in the rate of LPL-mediated lipolysis of TG-rich lipoproteins may lead to differences in HDL apolipoprotein fractional catabolic rate. (J. Clin. Invest. 1990. 86:463-473.)

Probucol Enhances Selective Uptake of HDL-Associated Cholesteryl Esters In Vitro by a Scavenger Receptor B-I–Dependent Mechanism

“…Each 2-pool model had a circulating pool in equilibrium with a noncirculating pool. 33 In each case, it was confirmed that 2 pools fit the data significantly better than did a 1-pool model; a third pool was not required for any study.…”

Endotoxin and cytokines decrease serum levels and extra hepatic protein and mRNA levels of cholesteryl ester transfer protein in syrian hamsters.

“…The decrease in HDL cholesterol levels may be linked to the increase in serum triglycerides as hypertriglyceridemia is often associated with decreased HDL cholesterol levels (31)(32)(33). CETP facilitates the exchange of cholesterol ester in HDL for VLDL triglyceride, thus the abundant VLDL triglyceride in hypertriglyceridemia can promote this exchange and contribute to the decrease in HDL cholesterol levels.…”

Endothelial lipase

“…It is generally postulated that variation in plasma HDL-C levels are determined not by the rate at which they are produced, but rather by the rate of catabolism of their components. There are several known molecules that play a role in regulating plasma HDL-C levels (31), including HL (32)(33)(34)(35), LPL (36)(37)(38)(39)(40), lecithin:cholesterol acyl transferase (LCAT) (41,42), cholesterol ester transfer protein (CETP) (43), and phospholipid transfer protein (PLTP) (44). Intense study over the last few years has focused on the HDL particle in the context of reverse cholesterol transport and anti-oxidant properties, providing significant insights into the mechanism of HDL's antiatherogenic properties.…”