Activities of lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma of patients with low concentrations of HDL cholesterol.

Abstract

Previous investigations have shown that abnormalities in the postheparin plasma levels of the lipolytic enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL), are correlated with variations in plasma high-density lipoprotein cholesterol (HDL-C) levels. The present study was performed to determine correlations between the postheparin plasma activities of these two enzymes and HDL levels in a sizable number of subjects with low HDL-C levels. Two types of low-HDL subjects were investigated: 159 male subjects with low HDL-C (<40 mg/dL) and normal triglyceride (<250 mg/dL) levels (the low-HDL group) and 80 male subjects with low HDL-C (<40 mg/dL) and elevated triglyceride (>250 mg/dL) levels (the low-HDL/high-TG group). Postheparin plasma activities of LPL and HTGL were determined in these two groups, and these levels were compared with those obtained from 51 normolipidemic (normal-HDL) male subjects. Postheparin LPL activities were significantly lower in the low-HDL and low-HDL/high-TG groups (mean±SD, 9.9±2.9 and 10.4+3.0 mmol/h per liter, respectively; P<.001 for both) compared with the normal-HDL group (12.5±3.7 mmol/h per liter). Conversely, postheparin HTGL activities were significantly higher in the low-HDL and low-HDL/high-TG groups (39.3+16.2 and 44.4+16.7 mmol/h per liter, respectively; P<.001 for both) compared with the normal-HDL group (29.7±11.3 mmol/h per liter). Consequently, mean LPL/HTGL ratios were markedly lower in the two low-HDL groups compared with the normal-HDL group. Within each group, analysis revealed no specific relationships between the enzyme activities and potential modifying factors (cigarette smoking and /3-adrenergic blocking agents). When subjects from each group who were neither smokers nor taking ^-blockers were compared, HTGL activities, but not LPL activities, were significantly different for the low-HDL groups compared with the normal-HDL group. The results of this study suggest that high HTGL activity and low LPL activity are both important contributors to low HDL levels in both normotriglyceridemic and hypertriglyceridemic subjects. However, in the absence of potential modifying factors, high HTGL activity appears to be the major change in lipolytic enzymes associated with HDL levels. (Arteriosclerosis reduce HDL levels. In other patients, raised serum triglycerides (TGs) appear to underlie low HDL levels. 910 The mechanisms by which these various factors cause low HDL concentrations are not fully understood. Moreover, a substantial number of people manifest low HDL levels without any evidence of these secondary factors. Recent reports 11 "14 indicate that most patients with low HDL levels have enhanced catabolism of apolipoprotein (apo) A-I, the major apolipoprotein of HDL, but whether this anomaly is directly responsible for low HDL levels is not known. On the other hand, several lines of evidence implicate abnormalities in the two endothelial lipolytic enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL), as direct causes of low HDL...

Severe Hypoalphalipoproteinemia in Mice Expressing Human Hepatic Lipase Deficient in Binding to Heparan Sulfate Proteoglycan

“…In humans, high plasma HL activity (measured using postheparin samples) is associated with reduced HDL cholesterol and small HDL particles (42). Conversely, genetic HL deficiency is associated with modestly elevated HDL cholesterol and large HDL particles (43,44).…”

“…2A), ruling out the possibility that hHLmt expression suppresses LPL-mediated lipolysis. It should be noted that unlike hHL, the post-heparin activity of which is negatively correlated with plasma HDL concentrations, post-heparin plasma LPL activity is directly correlated with HDL cholesterol levels (42). Expression of a heparin binding-deficient human LPL in mice results in elevated triglyceride and cholesterol associated with very low density lipoproteins (49).…”

Insulin resistance and abnormal albumin excretion in non-diabetic first-degree relatives of patients with NIDDM

“…Free apo A-I is cleared by kidneys and this could be accentuated by an abnormal AER. Blades et al [45] have reported that a high hepatic li-pase activity is associated with low HDL but normal VLDL levels. In addition, there is evidence to suggest that insulin resistance may influence the activity of both lipoprotein and hepatic lipase enzymes [46,47].…”

Hepatic Lipase C514T Polymorphism and its Relationship with Plasma HDL-C Levels and Coronary Artery Disease in Koreans

“…The inverse relationship between hepatic lipase activity and plasma HDL-C (Blades et al, 1993), a well known protective factor against CAD (Gordon and Rifkind, 1989), and the positive association of hepatic lipase with small dense LDL-C (Zambon et al, 1993), a possible risk factor of CAD *To whom correspondence should be addressed. Tel: 82-2-760-2684; Fax: 82-2-762-9662 E-mail: ihchae@snu.ac.kr (Lamarche et al, 1997), have pointed towards the proatherogenic role of hepatic lipase.…”