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In vitro remodelling of plasma lipoproteins in whole plasma by lipoprotein lipase in primary and secondary hypertriglyceridaemia
Author(s) -
LEVY E.,
DECKELBAUM R. J.,
THIBAULT R. L.,
SEIDMAN E.,
OLIVECRONA T.,
ROY C. C.
Publication year - 1990
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1990.tb01880.x
Subject(s) - lipoprotein lipase , chylomicron , medicine , very low density lipoprotein , hepatic lipase , chemistry , endocrinology , lipoprotein , plasma lipoprotein , cholesterol , enzyme , biochemistry
. In patients with familial lipoprotein lipase deficiency (FLPL‐d) and glycogen storage disease type I (GSD‐I), hypertriglyceridaemia (1445 pM 247 and 1082 pM 312 mg dl ‐1 , n = 5 per group) was associated primarily with reduced extrahepatic lipoprotein lipase (LPL) activity (0.33 pM 0.33 and 1.69 + 0.38 μmol FFA ml ‐1 h ‐1 ) when compared with controls (4.83 pM 0.90). Hypercholesterolaemia was characterized by elevated LDL cholesterol (191 pM 30 and 344 pM 34 vs. 115 pM 5 mg dl ‐1 in controls P <0.01) and low HDL cholesterol (12 pM 2 and 22 pM 2 vs. 56 pM 3 in controls, P < 0.001). In order to ascertain the role of LPL in the interconver‐sion and remodelling of lipoproteins in these disorders, we analysed lipid and lipoprotein profiles before and following in vitro incubation of patient plasma with purified milk LPL (EC 3.1.1.34) for 6 h at 37d̀C. The efficiency of exogenous LPL in vitro was demonstrated by the extent of hydrolysis of chylomicrons and of VLDL‐TG in both groups. Concomitant with the disappearance of TG‐rich lipoprotein particles, a consistent per cent increment of IDL (99.2 pM 30.8 and 43.9pM70.5), LDL (152.8 pM 36.2 and 137.0 pM 36.1) and of HDL 2 (144.8 pM 29.4 and 99.8 pM 18.7) was observed in both groups of patients. The enhancement of the latter fractions contrasted with the decline of HDL 3 mass concentration (25.4 pM 7.7 and 51.4pM5.8%), suggesting that a major shift of HDL 3 →HDL 2 occurs following in vitro lipolysis by LDL. Simultaneous compositional and morphological changes of individual lipoprotein particles were noted, confirming the dynamic movement and exchange of neutral lipids and proteins. Specificity of LPL results was demonstrated by experiments in which incubation of the whole plasma at 37d̀C without exogenous lipolytic enzyme did not cause any substantial changes. The present study, therefore, demonstrates a correction of the major lipoprotein abnormalities associated with FLPL‐d and GSD‐I by exogenous LPL. No substantial difference was noted between primary (FLPL‐d) and secondary (GSD‐I) hyperlipidaemias. These studies allow us to conclude that a simple in vitro system, utilizing an exogenous source of LPL and plasma from patients, may serve as a suitable model for the study of the metabolic relationships of lipoproteins. However, in view of the fact that the extent of lipolysis achieved in vitro did not differ between FLPL‐d and GSD‐I, it may not be able to separate primary from secondary hyperlipaemias.,