Effect of hepatic lipase on LDL in normal men and those with coronary artery disease.

Abstract

Hepatic triglyceride lipase (HL) is thought to play a role in the formation of low density lipoproteins (LDLs) from small very low density lipoproteins (VLDLs) and intermediate density lipoproteins (IDLs).To analyze the possible physiological role of HL in determining LDL buoyancy, size, and chemical composition, HL activity and LDL were studied in 21 patients with coronary artery disease (CAD) and 23 normolipidemic subjects. In both groups, LDL buoyancy and size were inversely associated with HL activity levels. The effect of HL on LDL size was comparable in CAD patients and in normolipidemic subjects. HL appeared to influence LDL lipid composition primarily by affecting the surface lipid components. The free cholesterol content of LDL particles was highly correlated with HL activity in both CAD and normolipidemic individuals. The free cholesterol to phospholipid ratio in LDL particles correlated with HL in both CAD and normolipidemic subjects. When the individuals were separated according to their LDL subclass patterns, pattern B subjects had significantly higher HL than pattern A subjects in both CAD and normolipidemic groups. LDL may take place. 9 The strongest evidence supporting the role of HL in LDL formation comes from studies performed on human and animal models with HL deficiency. -14 In these studies, low HL activity was associated with larger and more buoyant LDL particles, often extending into the IDL density range.To further examine the possible involvement of HL in determining the physical characteristics of LDL, the compositional and physical properties of LDL were examined in relation to HL activity levels in CAD patients and normolipidemic subjects. Methods SubjectsTwenty-one men aged 50.2 ±9 (mean±SEM) years and with elevated apolipoprotein (apo) B plasma levels (>125 mg/dl), a family history of CAD, and evidence of coronary atherosclerosis by coronary arteriography 3 were selected. All subjects were participants in a clinical intervention trial of intensive drug therapy for CAD; blood samples for the present study were drawn at a protocol time point 6 weeks after discontinuing lipidlowering therapy, at which time all LDL and apo B-related measurements had returned to pretreatment baseline levels.3 Two subjects were taking /J-blockers at the time of the present study. Dietary advice was given according to the American Heart Association's step I and II diets.3 Patients with diabetes; severe hypertension; cancer; or liver, thyroid, or kidney diseases were excluded.An additional 23 Caucasian men aged 33 ±2 years were recruited by advertisement and were paid to by guest on May 11, 2018 http://atvb.ahajournals.org/ Downloaded from

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

“…Circulating VLDLs are hydrolysed by two lipolytic enzymes, lipoprotein lipase and hepatic lipase. Both a decrease in lipoprotein lipase and an increase in hepatic lipase activity have previously been shown to be associated with the accumulation of pro-atherogenic small dense LDL particles, a lipoprotein composition that is particularly evident in the presence of increased VLDL concentrations [17,18]. Consistent with the above, we found an independent association between RPB4 levels and hepatic lipase activity in patients with type 2 diabetes and in those with CAD.…”

Lipoprotein distribution and composition in obesity: their association with central adiposity

“…38±40 Their origins are unclear, although the lipolytic action of hepatic lipase on LDL enriched in triglycerides due to the activity of lipid transfer protein, has been implicated. 16,41 What remains uncertain is the extent to which these lipoprotein particles may play an active role in the atherogenic process. Numerous studies have demonstrated a negative relationship between obesity and the cholesterol component of HDL.…”

A Hepatic Lipase Gene Promoter Polymorphism Attenuates the Increase in Hepatic Lipase Activity With Increasing Intra-abdominal Fat in Women

“…Higher HL activity increases the conversion of HDL 2 to HDL 3 9,10 and the conversion of large, buoyant LDL to small, dense LDL. 14 The link between IAF and HDL 2 -C metabolism appears to be mediated, at least in part, by hepatic lipase. There is an additional influence of IAF on LDL density beyond the effect of hepatic lipase, perhaps by altering the synthesis of TG-rich lipoproteins.…”

“…13 HL also catalyzes the hydrolysis of triglyceride and phospholipid in large, buoyant LDL forming small, dense more atherogenic LDL particles. 14 Increased risk of premature coronary artery disease (CAD) has been shown to be associated with the presence of small, dense LDL particles. [15][16][17][18][19] Similarly, low HDL-C is another major risk factor for CAD.…”