RELATIONS BETWEEN PLASMA-LIPIDS AND POSTHEPARIN PLASMA LIPASES AND VLDL AND LDL SUBFRACTION PATTERNS IN NORMOLIPEMIC MEN AND WOMEN

Citation
Ce. Tan et al., RELATIONS BETWEEN PLASMA-LIPIDS AND POSTHEPARIN PLASMA LIPASES AND VLDL AND LDL SUBFRACTION PATTERNS IN NORMOLIPEMIC MEN AND WOMEN, Arteriosclerosis, thrombosis, and vascular biology, 15(11), 1995, pp. 1839-1848
Citations number
34
Categorie Soggetti
Cardiac & Cardiovascular System","Peripheal Vascular Diseas
ISSN journal
10795642
Volume
15
Issue
11
Year of publication
1995
Pages
1839 - 1848
Database
ISI
SICI code
1079-5642(1995)15:11<1839:RBPAPP>2.0.ZU;2-I
Abstract
VLDL(1), VLDL(2), IDL, and LDL and its subfractions (LDL-I, LDL-II, an d LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin , and glucose. Concentrations of VLDL(1) and VLDL(2) rose as plasma tr iglycerides (TGs) increased across the normal range, but the associati on of plasma TGs with VLDL(1) showed a steeper slope than that of VLDL (2) (P < .001). Plasma TG level was the most important determinant of LDL subfraction distribution. The least dense species, LDL-I, decrease d as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG lev el in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg /dL. In contrast, within this TG range the LDL-III concentration was l ow (approximate to 30 mg/dL) and changed little. As plasma TGs rose fr om 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentrat ion in men (r = - .45, P < .001) but not in women (r = -.1, NS). Conve rsely, above the TG threshold of 1.3 mmol/L there was a steeper rise i n LDL-III concentrations in men than in women (P < .001); 42% of the m en had an LDL-III in the range associated with high risk of heart dise ase (> 100 mg lipoprotein/dL plasma) compared with only 17% of the wom en. Other influences on the LDL subfraction profile were the activitie s of lipases and parameters indicative of the presence of insulin resi stance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL sub fraction profile in men, but in women it was correlated with LDL-III ( r = .39, P = .001) and remained a significant predictor in multivariat e analysis. Increased waist/hip ratio, fasting insulin, and glucose we re correlated negatively with LDL-I and positively with LDL-III, prima rily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the follo wing model for the generation of LDL-III. Subjects develop elevated le vels of large TO-rich VLDL(1) for a number of reasons, including failu re of insulin action. The increase in the concentration of VLDL(1) exp ands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between li poprotein particles), promotes the net transfer of TGs into LDL-II, th e major LDL species. A hepatic lipase activity in the male range (due possibly to androgen/estrogen imbalance in women) is then required to lipolyze TO-enriched LDL-II and to generate a concentration of small, dense LDL-III that exceeds the risk limit of 100 mg/dL.