LCAT-dependent conversion of prebeta1-HDL into alpha-migrating HDL is severely delayed in hemodialysis patients.
Prebeta1-HDL is a minor HDL subfraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37 degrees C incubation, plasma prebeta1-HDL decreases over time due to its conversion to alpha-migrating HDL by lecithin:cholesterol acyltransferase (LCAT). This conversion may be delayed in hemodialysis patients who have decreased LCAT activity. To clarify whether LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is delayed in hemodialysis patients, prebeta1-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37 degrees C incubation with and without the LCAT inhibitor. It was found that the baseline prebeta1-HDL concentration in hemodialysis patients was more than twice that in the controls (44.9 +/- 21.4 versus 19.8 +/- 6.7 mg/L apoAI; P < 0.001). After 2-h incubation, the LCAT-dependent decrease in prebeta1-HDL in hemodialysis patients was about one-third of that in the controls (30 +/- 27 versus 97 +/- 17% of baseline; P < 0.01). The LCAT-dependent rate of decrease in prebeta1-HDL levels (DR(prebeta1)) was the same for samples from hemodialysis patients exhibiting normal (> or =1.03 mmol/L) and low HDL-cholesterol levels (32 +/- 32 versus 28 +/- 23% of baseline; NS). DR(prebeta1) was positively correlated with LCAT activity (r = 0.617; P < 0.001). In conclusion, the LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of prebeta1-HDL may accelerate atherosclerosis in hemodialysis patients.
Miida
Takashi
T
Division of Clinical Preventive Medicine, Department of Community Preventive Medicine, Niigata University, Graduate School of Medical and Dental Sciences, Japan. miida@med.niigata-u.ac.jp
Miyazaki
Osamu
O
Hanyu
Osamu
O
Nakamura
Yuichi
Y
Hirayama
Satoshi
S
Narita
Ichiei
I
Gejyo
Fumitake
F
Ei
Isei
I
Tasaki
Kazuyuki
K
Kohda
Yutaka
Y
Ohta
Takashi
T
Yata
Syogo
S
Fukamachi
Isamu
I
Okada
Masahiko
M
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006023:Glycoproteins; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D007124:Immunoenzyme Techniques; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000628:therapy; D008075:Lipoproteins, HDL / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D006435:Renal Dialysis
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase