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Study On Relationship Between Blood Lipid Levels And HDL Subclasses Distribution

Posted on:2007-01-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Y YangFull Text:PDF
GTID:1114360242464057Subject:Biochemistry and Molecular Biology
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PartⅠRelationship between plasma lipid concentrations and HDL subclassesⅠ. Relationship between plasma lipid concentrations and HDLsubclasses in humanBackground: It is generally accepted that different high-densitylipoprotein (HDL) subclasses have distinct but intcrrelated metabolic functions.HDL is known to directly influence the atherogenic process and changes inHDL subclasses distribution may be related to the incidence and prevalence ofatherosclerosis.Methods: Apo-AI contents(mg/l) of plasma HDL subclasses weredetermined by 2-dimensional gel electrophoresis coupled withimmunodetection for apo-AI. Four hundred forty-two Chinese adults subjectsaged 33 to 78 years were assigned to different groups according to the thirdReport of NCEP (ATPⅢ) guidelines. The subjects were first divided into 2groups, normal and high TG, then further classified by plasma TC, HDL-Cand LDL-C concentrations. The subjects were also divided into TC desirableand TC high groups.Results: Apo-A contents of preβ1-HDL were higher while HDL2b werelower in high TG subjects vs. the corresponding normal TG subjects accordingto plasma TC and LDL-C concentrations. With the increase of plasma TCconcentrations, apo-AI contents of preβ1-HDL were significantly higher inhigh TC subgroup vs. TC desirable subgroup in normal TG subjects. With thedecrease of HDL-C concentrations, apo-AI contents of HDL2b tended to decrease in normal TG subjects. And, with the increases of LDL-Cconcentration, in normal TG subjects, apo-AI contents of preβ1-HDL andHDL3b were significantly higher and those of HDL2b were significantly lowerin very high LDL-C subgroup vs. LDL-C optimal subgroup. On the other hand,apo-AI contents of prehl-HDL and HDL3a were significantly higher, whileHDL2a and HDL2b were significantly lower in high TG and very high TGsubgroup vs. normal TG subgroup within either TC desirable or TC highsubjects. In a multivariate linear regression model, TG and TC concentrationswere all associated independently and positively with high preh1-HDL;however, HDL-C were inversely associated with high preh1-HDL. And TGand TC concentrations were all associated independently and negatively withlow HDL2b, but HDL-C and apo-AI were positively associated with lowHDL2b.Conclusions: With the increase of plasma TG, TC, LDL-C or thedecrease of plasma HDL-C concentrations, there was a general shift towardsmaller-sized HDL, which, in turn, indicates that reverse cholesterol transportmight be weakened and HDL maturation might be abnormal. Plasma TGconcentration is a more important factor than TC concentration on the changesof HDL subclass distribution. Moreover, when TG is normal and HDL-Cdecreased, large-size HDL particles tended to decrease. Ⅱ. Alterations of HDL subclasses in different lipid levels of men andwomenBackground: It is generally accepted that different high-densitylipoprotein(HDL) subclasses have distinct and correlative metabolic functions.HDL is known to directly influence the atherogenic process and changes inHDL subclasses distribution may be related to the incidence and prevalence ofatherosclerosis.Materials and Method: The apoA-Ⅰconcentrations(mg/L) of plasmaHDL subclasses were determined by two-dimensional gel electrophoresiscoupled with immunodetection for apoA-Ⅰ. The subjects were classified bygender and plasma levels of triglyceride (TG), low densitylipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C)respectively.Results: With the increase of plasma TG level, both in men and women,apoA-Ⅰconcentrations of preβ1-HDL and HDL3a were significantly higherwhile HDL2a and HDL2b were significantly lower. Similarly, with the increaseof plasma LDL-C level, apoA-Ⅰconcentrations of preβ1-HDL, HDL3c(in men)and HDL3b were significantly higher while apoA-Ⅰconcentrations of HDL2bwere significantly lower. And with the decrease of plasma HDL-C,apoA-Ⅰconcentrations of preβ1-HDL, HDL3Cand HDL3b were significantlyhigher while apoA-Ⅰconcentrations of HDL2a and HDL2b were significantlylower. In addition, apoA-Ⅰconcentrations of preβ1-HDL was significantlylower in women TG<1.7 mmol/L and TG 1.7~2.5 mmol/L vs. men groups.And apoA-Ⅰconcentrations of HDL2b in women LDL-C<2.6 mmol/L, LDL2.6~3.3 mmol/L and HDL-C 1.0~1.6 mmol/L, HDL-C<1.0 mmol/L groupswere significantly higher than men groups.Conclusion: In all subjects, with the increase of TG, LDL-C anddecrease of HDL-C, the particle size of HDL shifted towards smaller sizes,which, in turn, indicates that the maturation of HDL may be impeded in those subjects with abnormal lipids profile. In women HDL particles are bigger thanthe men, which potentially result in the gender differences in CHD risk factorsand susceptibility to atherosclerosis. PartⅡSex and age differences in HDL subclass distribution in a ChinesepopulationBackground: There is limited information regarding Chinese populationsex and age differences in HDL subclasses containing preβ1-HDL, preβ2-HDL,HDL3c, HDL3b, HDL3a, HDL2a, and HDL2b.Method: The apoA-Ⅰcontents(mg/L) of plasma HDL subclasses weredetermined by two-dimensional gel electrophoresis coupled withimmunodetection for apoA-Ⅰ. The 512 Chinese people (303 men, 209 women)were classified by gender, age group and pre/post-menopausal respectively.Pre-menopausal women were 81 and post-menopausal women were 128.Results: Concentrations of plasma TG, apoCⅡ, apoE andapoA-Ⅰcontents of preβ1-HDL were significantly lower, whereas HDL-C andHDL2b appeared to higher in women than in men for ages 30 to 39, 40 to 49groups. Body mass index, and concentrations of plasma TG, TC, apoB100,apoCⅡ, apoE, apoA-Ⅰcontents of preβ1-HDL, preβ2-HDL and HDL3bincreased, whereas HDL-C and HDL2b decreased with age. ApoA-Ⅰcontentsof preβ1-HDL and HDL3b were significantly higher and HDL2a and HDL2bwere significantly lower in pre-menopausal women than in post-menopausalwomen as well as in men. Moreover, HDL particle sizes, especiallypreβ1-HDL were positively correlated and HDL2b was negatively correlatedwith TG and TC in men and women. Preβ1-HDL was negatively correlatedand HDL2b was positively correlated with HDL-C in men.Conclusion: Small, dense HDL subclass particles predominated amongmen, and the apoA-Ⅰcontents of large-sized HDL in men were lower thanthat in women; however, the sex difference narrowed with age. Older peoplehave the higher small-sized and lower lager-sized HDL contents.Post-menopausal women have higher small-sized and lower lager-sized HDLsubclasses than pre-menopausal women. PartⅢAlteration of the mRNA Expression of Key Enzymes in Lipid Metabolismin Liver of Hypertriglyceridemic RatsBackground: In hypertriglyceridemia in human, the particle size of HDLshifted towards smaller size. There are various key enzymes in liver involvedwith the process of HDL maturation. Therefore, we study the levels of apoA-Ⅰ,apoA-Ⅴ, LPL, HL, LCAT, and SR-B1 mRNA expression inhypertriglyceridemic rats.Method: Hypertriglyceridemic rats were fed with a prepared highcarbohydrate diet for 3 days. The levels of apoA-Ⅰ, apoA-Ⅴ, LPL, HL, LCAT,and SR-B1 mRNA expression were measured by using RT-PCR, and apoA-Ⅰprotein expression was quantified by employing Western blot analysis.Results: High carbohydrate diet induced significant elevation of serumTG while decrease of the levels of serum HDL-C than control diet group. Thelevels of apo-AⅠboth in mRNA and protein expression significantly loweredin high carbohydrate diet group. Moreover, although the variation of mRNAexpression of LCAT, LPL and HL failed to reach significance, data revealedthat compared with control group the mRNA levels of LCAT and LPL tended to lower whereas HL tended to increase. In addition, the other genes includingapoA-Ⅴand SR-B1 showed no obvious changes.Conclusion: The levels of apo-AⅠboth in mRNA and protein expressionsignificantly lowered in high carbohydrate diet groups, and decrease of apoA-Ⅰexpression may induce decrease of HDL-C concentration.
Keywords/Search Tags:Apo-AI containing HDL subclasses, Triglyceride, Total cholesterol, High-density lipoprotein-cholesterol, Low-density lipoproteincholesterol, Two-dimensional gel electrophoresis-immunodetection, ApoA-Ⅰcontaining HDL subclasses
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