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1.
J Biol Chem ; 276(29): 26898-905, 2001 Jul 20.
Article in English | MEDLINE | ID: mdl-11325961

ABSTRACT

Phospholipid transfer protein (PLTP) remodels high density lipoproteins (HDL) into large and small particles. It also mediates the dissociation of lipid-poor or lipid-free apolipoprotein A-I (apoA-I) from HDL. Remodeling is enhanced markedly in triglyceride (TG)-enriched HDL (Rye, K.-A., Jauhiainen, M., Barter, P. J., and Ehnholm. C. (1998) J. Lipid. Res. 39, 613-622). This study defines the mechanism of the remodeling of HDL by PLTP and determines why it is enhanced in TG-enriched HDL. Homogeneous populations of spherical reconstituted HDL (rHDL) containing apoA-I and either cholesteryl esters only (CE-rHDL; diameter 9.3 nm) or CE and TG in their core (TG-rHDL; diameter 9.5 nm) were used. After 24 h of incubation with PLTP, all of the TG-rHDL, but only a proportion of the CE-rHDL, were converted into large (11.3-nm diameter) and small (7.7-nm diameter) particles. Only small particles were formed during the first 6 h of incubation of CE-rHDL with PLTP. The large particles and dissociated apoA-I were apparent after 12 h. In the case of TG-rHDL, small particles appeared after 1 h of incubation, while dissociated apoA-I and large particles were apparent at 3 h. The composition of the large particles indicated that they were derived from a fusion product. Spectroscopic studies indicated that the apoA-I in TG-rHDL was less stable than the apoA-I in CE-rHDL. In conclusion, these results show that (i) PLTP mediates rHDL fusion, (ii) the fusion product rearranges by two independent processes into small and large particles, and (iii) the more rapid remodeling of TG-rHDL by PLTP may be due to the destabilization of apoA-I.


Subject(s)
Carrier Proteins/metabolism , Lipoproteins, HDL/metabolism , Membrane Proteins/metabolism , Phospholipid Transfer Proteins , Epitope Mapping , Humans , Kinetics , Lipoproteins, HDL/chemistry , Protein Binding , Protein Denaturation , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Triglycerides/metabolism
2.
Am J Dis Child ; 147(7): 732-6, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8322742

ABSTRACT

OBJECTIVE: To determine abnormalities of cholesterol metabolism in children with acute rheumatic fever (ARF). DESIGN: Cross-sectional study and prospective study. SETTING: Pediatric ward of the Khon Kaen (Thailand) University Hospital. PARTICIPANTS: Forty-six confirmed patients with ARF (during the acute and recovery phases of disease), 51 siblings, and 92 age- and sex-matched control children. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Serum samples of these children were studied for serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels and liver function tests. No significant differences were found in mean serum total cholesterol levels (3.68 +/- 0.86 mmol/L [142.4 +/- 33.3 mg/dL] vs 3.75 +/- 0.67 mmol/L [145.0 +/- 25.8 mg/dL], 3.79 +/- 0.75 mmol/L [146.4 +/- 29.0 mg/dL], and 3.80 +/- 0.59 mmol/L [146.9 +/- 23.0 mg/dL]) or mean triglyceride levels (1.19 +/- 0.33 mmol/L vs 1.16 +/- 0.51, 1.12 +/- 0.37, and 1.07 +/- 0.41 mmol/L) (during ARF vs after ARF, sibling, and age- and sex-matched control children, respectively). The children with ARF had significantly lower mean levels of high-density lipoprotein cholesterol and of albumin than did the other groups (analysis of variance, P < .0001). In the ARF group, high-density lipoprotein cholesterol and albumin levels varied inversely with the clinical severity of carditis, while, in contrast, triglyceride and alkaline phosphatase levels varied with the clinical severity of carditis. CONCLUSIONS: This study confirms abnormalities of cholesterol metabolism in ARF. Hepatic dysfunction associated with the clinically detectable severity of carditis or inflammation might explain the observed differences in serum high-density lipoprotein cholesterol and triglyceride levels in these children.


Subject(s)
Cholesterol/blood , Rheumatic Fever/blood , Acute Disease , Adolescent , Child , Child, Preschool , Cholesterol/metabolism , Diet , Female , Humans , Liver/metabolism , Liver Function Tests , Male , Nutritional Status , Prospective Studies
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