Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient.
A female patient (64 years of age; body mass index, 26) had a markedly and relatively low low-density lipoprotein-cholesterol (LDL-C) level (97 mg/dl) despite high serum total cholesterol (TC) (331 mg/dl) and triacylglyceride levels (307 mg/dl). Since the expected LDL-C was 222 mg/dl, there was a significant difference between the calculation and measurement based on direct enzyme assay. Only 30% of serum cholesterol was associated with LDL-C in this patient. To determine the basis for the markedly low LDL-C/TC ratio, we isolated and analyzed lipoproteins from the patient as well as age- and gender-matched controls. The patient had lowered serum CETP activity and elevated paraoxonase activity with GOT and GPT values in the normal range. The very low-density lipoprotein particles from the patient were larger than those of the controls and enriched with lipid and protein, while the LDL from the patient (LDL-P) had a lower particle number and protein content than the controls. The LDL-P was more resistant to cupric ion-mediated oxidation. HDL2 from the patient (HDL2-P) had highly enhanced paraoxonase activity and antioxidant ability. The patient had a 1.5-fold higher level of apolipoprotein (apo) A-I expression in HDL2. ApoA-I in HDL2 and HDL3 from the patient showed no fragmentation, while the control had fragmented bands (17 and 21 kDa) in the HDL. The HDL2-P also had a larger particle size and greater protein content with less lipid content. HDL3-associated cholesteryl ester transfer protein was reduced in the patient, although the particle size was similar to the controls. In conclusion, a patient who had a markedly lower LDL-C/TC ratio despite hyperlipidemia associated with higher paraoxonase activity, higher apoA-I level and lower CETP activity without fragmentation of apoA-I in the HDL fraction is presented. The enhanced antioxidant and anti-inflammatory activity of HDL might contribute to the low LDL-C/TC ratio in this patient.
Lee
Ji-Hye
JH
School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea.
Park
Jung-Heun
JH
Lee
Sang-Hak
SH
Kim
Jae-Ryong
JR
Cho
Kyung-Hyun
KH
D000975:Antioxidants / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D015153:Blotting, Western; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism / Q000648:ultrastructure; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000201:enzymology*; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications* / Q000201:enzymology*; D007501:Iron / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction
D000975:Antioxidants; D016632:Apolipoprotein A-I; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007501:Iron; D043303:Aryldialkylphosphatase