The value and distribution of high-density lipoprotein subclass in patients with acute coronary syndrome.

BACKGROUND: High-density lipoprotein (HDL) enhances cholesterol efflux from the arterial wall and exhibits potent anti-inflammatory and anti-atherosclerosis (AS) properties. Whether raised HDL levels will clinically benefit patients with acute coronary syndrome (ACS) and the value at which these effects will be apparent, however, is debatable. This study examined the HDL subclass distribution profile in patients with ACS. METHODS: Plasma HDL subclasses were measured in 158 patients with established ACS and quantified by two-dimensional gel electrophoresis and immunoblotting. ACS diagnosis was based on symptoms of cardiac ischemia, electrocardiogram (ECG) abnormalities, speciality cardiac enzyme change along with presence of coronary heart disease (CHD) on coronary angiography. RESULTS: The small-sized preß1-HDL, HDL3b, and HDL3a levels were significantly higher, and the large-sized HDL2a and HDL2b levels were significantly lower in patients with ACS than in those with stable angina pectoris (SAP) and in normal control subjects. Meanwhile, with an elevation in the low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP), and the reduction in the high density lipoprotein cholesterol (HDL-C) levels, the HDL2b contents significantly decreased and the preß1-HDL contents significantly increased in patients with ACS. The correlation analysis revealed that the apolipoprotein (apo)A-I levels were positively and significantly with all HDL subclasses contents; plasma total cholesterol (TC) and fasting plasma glucose (FPG) levels were inversely associated with HDL2a, and HDL2b. Moreover, the FPG levels were positively related to HDL3c, HDL3b, and HDL3a in ACS patients. CONCLUSION: The HDL subclass distribution profile remodeling was noted in the patients with ACS. Plasma lipoprotein and FPG levels, BP, and BMI play an important role in the HDL subclass metabolism disorder for patients with ACS. The HDL subclass distribution phenotype might be useful as a novel biomarker to assist in the risk stratification of patients with ACS.

[Studies of influences of blood glucose controlling on the changes of lipid profiles, ApoB100, ApoAI and HDL subclass of newly diagnosed type 2 diabetes].

This study was aimed to observe if the lipid profiles, apoprotein B100 (ApoB100), ApoAI, high density lipoprotein (HDL) and its subclasses could be improved by controlling the blood glucose. Fifty-three patients with newly diagnosed type 2 diabetic were divided into four groups, diet and exercise group (n = 13), continuous subcutaneous insulin infusion (CSII) group (n = 14), multiple daily insulin injection group (MDI, n = 13), and oral hypoglycaemic agents group (n = 13). Fasting blood glucose (FPG), glycated hemoglobin A1c (HbA1c), lipid profiles, ApoB100, ApoAI and HDL subclasses were measured at beginning and a month later. Forty-three patients finished the testing. The levels of FPG, HbA1c, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and ApoB100 were decreased significantly (P < 0.05) in all groups, and ApoAI/ApoB100 increased obviously (P < 0.05). Comparatively matured HDL subclasses such as HDL2b were increased (P < 0.05), and comparatively infantile HDL subclasses such as HDL3b were decreased (P < 0.05). Therapy with hyperglycemic agents improved TG, TC, LDL-C, ApoB100, ApoAI/ApoB100, and HDL2b significantly (P < 0.05), but intervention with the diet and exercise group alone did not improve lipid profiles, apolipoproteins, and HDL subclasses (P > 0.05). Meanwhile, therapy with insulin intensive therapy (MDI, CSII) group had the most powerful effect on decreasing ApoB100 concentration (P < 0.05). The results suggested that lipid profiles, apolipoproteins, and quantity and quality of HDL subclasses might be improved by blood glucose controlling.

Statin treatment improves plasma lipid levels but not HDL subclass distribution in patients undergoing percutaneous coronary intervention.

Despite the established efficacy of statin therapy, the risk of cardiovascular events remains high in many patients. We examined high-density lipoprotein (HDL) subclass distribution profiles among statin-treated coronary heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). Plasma HDL subclasses were measured in 85 patients with established CHD and quantified by two-dimensional gel electrophoresis and immunoblotting. In CHD patients with statin treatment, the mean value of total cholesterol (TC) reached the desirable level and the triacylglycerol level (TAG) was borderline high. Moreover, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoproteinA-I, and apolipoproteinB-100 levels in these patients resembled those in normolipidemic healthy subjects. The HDL subclass did not show a normal distribution and was characterized by the lower large-sized HDL(2b) contents and higher contents of small-sized preß1-HDL in CHD patients, compared to those in normolipidemic control subjects. Multiple stepwise regression analysis revealed that the severity of coronary stenosis, determined by the Gensini Score, was significantly and independently predicted by HDL(2b) and HDL(3b). Statin therapy was effective in modifying plasma lipids levels, but not adequate as a monotherapy to normalize the HDL subclass distribution phenotype of patients with CHD undergoing PCI. The HDL subclass distribution may aid in risk stratification, especially in patients with CHD and therapeutic LDL-C and HDL-C levels.

High-density lipoprotein subclass and particle size in coronary heart disease patients with or without diabetes.

BACKGROUND: A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes. METHODS: Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection. RESULTS: Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL(3b) and (3a)) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL(2b+preß2), and HDL(2a) were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The preß1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL(2a), and HDL(2b+preß2). CONCLUSIONS: The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.

Characteristics of high-density lipoprotein subclasses distribution for subjects with desirable total cholesterol levels.

BACKGROUND: To investigate alteration of high density lipoproteins (HDL) subclasses distribution in different total cholesterol (TC) levels, mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms. METHODS: ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection. 486 Chinese Adults subjects were assigned to different TC groups according to the third Report of NCEP (ATP-III) guidelines. RESULTS: The increase in contents of small preß1-HDL, HDL3c, HDL3b, and HDL3a particles clustered and reduce in HDL2b with increased of TC. The distribution of HDL subclasses have shown abnormality characterized by the lower HDL2b (324.2 mg/L) contents and the higher preß1-HDL (90.4 mg/L) contents for desirable TC Chinese subjects. Among 176 desirable TC subjects, 58.6% subjects with triglyceride (TG)<2.26 mmol/L, 61.2% subjects with HDL-C≥1.03 mmol/L and 88.6% subjects with low density lipoprotein cholesterol(LDL-C)<3.34 mmol/L, and the profile of HDL subclasses distribution for above these subjects was reasonable. CONCLUSIONS: The particles size of HDL subclasses shifted towards smaller with increased TC levels. The TC was liner with HDL2b contents and those can be reduced 17 mg/L for 0.5 mmol/L increment in TC levels. The HDL subclasses distribution phenotype was not expectation for Chinese Population with desirable TC levels. Thus, from the HDL subclasses distribution point, when assessing the coronary heart disease(CHD) risk not only rely on the TC levels, but also the concentrations of TG, HDL-C and LDL-C must considered in case the potential risk for desirable TC subjects with other plasma lipids metabolism disorders.

The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution.

OBJECTIVE: To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. METHODS: Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. RESULTS: Contents of preß1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preß1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of preß1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. CONCLUSIONS: The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preß1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.

The relationship between high density lipoprotein subclass profile and plasma lipids concentrations.

HDL particles possess multiple antiatherogenic activities and the identification and differentiation of individual HDL subclasses may be useful in documentation and understanding of metabolic changes of different HDL subclasses. The major plasma lipids exist and are transported in the form of lipoprotein complexes. Hence, alterations in plasma lipids levels can interfere with the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. The research review major discussed the relationship between plasma lipids levels and HDL subclasses distribution. The general shift toward smaller size of HDL particle size in HTG, HCL and MHL subjects, and the changes were more prominent with the elevation of TG and TC levels which imply that HDL maturation might be abnormal and RCT pathway might be weaken, and these changes were more seriously in MHL subjects. Plasma contents of small sized HDL particles significantly higher, whereas those of large sized HDL particles were significantly lower with elevation of TG/HDL-C and TC/HDL-C ratios. Increased in the TC/HDL-C ratio alone did not influence the distributions of HDL subclasses significantly when the TG/HDL-C ratio was low (TG/HDL-C ≤ 2.5). Hence, the TG/HDL-C ratio might be more sensitive to reflect the alteration of HDL subclass distribution than the TC/HDL-C ratio. In LDL-C/HDL-C ≤ 2.3 group, the pattern of distribution in HDL subclass was in agreement with the normolipidemic subjects. Moreover, considering the relative ease of measuring TC/HDL-C, TG/HDL-C and LDL-C/HDL-C ratios, as opposed to measuring HDL subclasses, these 3 ratios together may be a good indicator of HDL subclass distribution. The protective effect of increased apoA-I levels against the reduction of HDL(2b) caused by elevated TG concentration. On one hand, plasma HDL-C and apoA-I appear to play a coordinated role in the assembly of HDL particles and the determination of their contents among the total subjects. On the other hand, the apoA-I level might be a more powerful factor than HDL-C to influence the distribution of HDL subclasses in hyperlipidemic subjects. At the same time, from point of HDL subclasses distribution, the plasma lipids, apos concentrations and apos ratios should be considered while assessing the CHD risk. Abnormality of HDL subclasses distribution may result in accelerated atherosclerosis, therapeutic normalization of attenuated antiatherogenic HDL function in terms of both particle number and distribution of HDL particles is the target of innovative pharmacological approaches to large-sized HDL particles rising, including enhanced apoA-I levels.

Association of the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and concentrations of plasma lipids with high-density lipoprotein subclass distribution in the Chinese population.

BACKGROUND: To evaluate the relationship between the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and HDL subclass distribution and to further examine and discuss the potential impact of LDL-C and HDL-C together with TG on HDL subclass metabolism. RESULTS: Small-sized prebeta1-HDL, HDL3b and HDL3a increased significantly while large-sized HDL2a and HDL2b decreased significantly as the LDL-C/HDL-C ratio increased. The subjects in low HDL-C level (< 1.03 mmol/L) who had an elevation of the LDL-C/HDL-C ratio and a reduction of HDL2b/prebeta1-HDL regardless of an undesirable or high LDL-C level. At desirable LDL-C levels (< 3.34 mmol/L), the HDL2b/prebeta1-HDL ratio was 5.4 for the subjects with a high HDL-C concentration (> or = 1.55 mmol/L); however, at high LDL-C levels (> or = 3.36 mmol/L), the ratio of LDL-C/HDL-C was 2.8 in subjects, and an extremely low HDL2b/prebeta1-HDL value although with high HDL-C concentration. CONCLUSION: With increase of the LDL-C/HDL-C ratio, there was a general shift toward smaller-sized HDL particles, which implied that the maturation process of HDL was blocked. High HDL-C concentrations can regulate the HDL subclass distribution at desirable and borderline LDL-C levels but cannot counteract the influence of high LDL-C levels on HDL subclass distribution.

[Antioxidants inhibit the oxidative modification of high density lipoproteins].

OBJECTIVE: To study the role and mechanism of antioxidants on inhibiting oxidative modification of high density lipoproteins (HDL). METHODS: Freshly prepared human plasma HDL was treated by incubation with copper ion, hyperchlorite or arterial wall cells. Compared to control, the test groups were treated with addition of different concentration of butylhydroxytoluene (BHT), vitamin C and vitamin E. Then, the relative electrophoretic mobility (REM), thiobarbituric acid-reactive substances (TBARS), ratio of lysolecithin to lecithin (LPC/PC), and lipoprotein moieties were investigated. RESULTS: BHT, vitamin C and vitamin E can significantly inhibit the increasing REM, TBARS, LPC/PC ratio and lipoprotein variation that induced by copper ion and hyperchlorite and arterial wall cells. But these antioxidants act on different manner. CONCLUSION: BHT, vitamin C and vitamin E can inhibit the oxidative modification of HDL and hence could be potential nutrients to prevent atherosclerosis.

Influence of apolipoproteinCII concentrations on HDL subclass distribution.

AIM: To demonstrate the interrelationship between plasma apolipoprotein(apo)CII concentrations and the pattern of high-density lipoprotein (HDL) subclass distribution. METHODS: ApolipoproteinA-I contents of plasma HDL subclasses were quantified by 2-dimensional gel electrophoresis associated with immunodetection in 504 Chinese subjects. RESULTS: Compared with subjects in the lowest tertile of the apoCII group, the contents of prebeta(1)- HDL, HDL(3b), and HDL(3a) were significantly higher than HDL(2a) and HDL(2b) in subjects in the middle and highest tertiles of the apoCII group. Moreover, regardless of whether apoB100 increased, prebeta(1)-HDL contents increased, but HDL(2b) fell when apoCII rose while, at any apoCII levels, HDL(2b) rose with the elevation of apoA-I. Additionally, a reduction in prebeta(1)-HDL (from 131.9 to 90.6 mg/L) but an increase in HDL(2b) (from 269.1 to 382.7 mg/L) with a rise in the apoCIII/CIi value (between 0.8 and 5.6) were also observed. CONCLUSION: The particle size of HDL become smaller with the increase of apoCII levels, implying that the efficiency of reverse cholesterol transport (RCT) was impaired and blocked the maturation of HDL. ApoCII might be an independent factor affecting the distribution of HDL subclasses. Further, the apoCIII/CII ratio correlated with the size of HDL particles.

Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution.

High-density lipoprotein (HDL) subclasses have different antiatherogenic potentials and functional properties. This work presents our findings and discussions on their metabolic implications on apolipoprotein (apo) C-III together with other apolipoprotein levels and HDL subclass distribution profile. Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 511 subjects. Concentrations of triglycerides and of apo B-100, C-II, and C-III were higher, whereas those of HDL cholesterol were lower, for subjects in the highest tertile of apo C-III levels group, which presented a typical hypertriglyceridemic lipid profile. Subjects in the middle and highest tertile of apo C-III levels groups had increased prebeta(1)-HDL, HDL(3c), HDL(3b) (only in the highest tertile of apo C-III group), and HDL(3a), but decreased HDL(2a) and HDL(2b) contents compared with subjects in the lowest tertile of apo C-III levels group. With the elevation of apo C-III together with apo C-II levels, contents of small-sized prebeta(1)-HDL increased successively and significantly; but those of large-sized HDL(2b) reduced successively and significantly. With a rise in apo C-III and apo A-I levels, those of prebeta(1)-HDL increased significantly. Moreover, subjects with high apo A-I levels showed a substantial increase in HDL(2b); on the contrary, HDL(2b) declined progressively and obviously for subjects in the low apo A-I levels with the elevation of apo C-III levels. Correlation analysis illustrated that apo C-III levels were positively associated with prebeta(1)-HDL, prebeta(2)-HDL, and HDL(3a). The particle size of HDL shifted toward smaller sizes with the increase of plasma apo C-III levels, and the shift was more remarkable when the elevation of apo C-III and apo C-II was simultaneous; and besides, higher apo A-I concentrations could modify the effect of apo C-III on HDL subclass distribution profile. Large-sized HDL(2b) particles decreased greatly for hypertriglyceridemic subjects who were characterized by elevated apo C-III and C-II accompanied with significantly lower apo A-I, which, in turn, blocked the maturation of HDL.

Relationship between plasma apolipoproteinB concentrations, apolipoproteinB/apolipoproeinA-I and HDL subclasses distribution.

BACKGROUND: To analyze the relationship between plasma apoB100 concentrations, apoB100/apoA-I ratio and the alteration of HDL subclasses distribution. METHODS: The apoA-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 506 subjects. RESULTS: The subjects in the highest tertile of apoB100 groups had significantly higher small-sized prebeta(1)-HDL, however lower large-sized HDL(2a), HDL(2b) than the subjects in the lowest tertile of apoB100 group. Furthermore, a significant down in the HDL(2b)/prebeta(1)-HDL values (from 6.8 to 1.6) with a rise in apoB100/apoA-I ratio (from 0.4 to 1.4) were observed. Compared to subjects with apoB100/apoA-I ratio<0.9, the subjects with apoB100/apoA-I ratio > or =0.9 had significantly higher small-sized prebeta(1)-HDL whereas lower HDL(3a), HDL(3b) and large-sized HDL(2a), HDL(2b.) Pearson correlation revealed that concentrations of apoB100 were positively correlated with prebeta(1)-HDL but negatively correlated with HDL(2a) and HDL(2b), and in multivariate analysis, all HDL subclasses were independently associated with the apoB100/apoA-I ratio. CONCLUSION: The apoB100 concentrations, especially apoB100/apoA-I ratio could reflect sensitively the alteration of HDL subclasses distribution. And HDL subclasses distribution characteristics of hyperlipidemic subjects appeared in the subjects with apoB100/apoA-I ratio > or =0.9, which indicated the efficiency of RCT was weakened and the maturation of HDL was blocked.

[Study on the protective effect of HDL subclasses against lipopolysaccharide].

AIM: To elucidate the anti-LPS effect of high-density lipoprotein (HDL) subclasses. METHODS: The pNF-kappaB-luc plasmid was transfected into HepG2 cells and the luciferase expression was obtained by the optimization of cell density, incubation time of transfected cells and stimulating concentration of LPS. The luciferase expression was examined in the cells treated with various stimulus including LPS, mixtures of HDL subclasses and LPS. The expression of TNF-alpha mRNA was detected RT-PCR. RESULTS: After LPS stimulation, HDL subclasses did not show obvious influence on the effect of LPS to stimulate the luciferase production. However, pre-incubation of cells or pre-incubation of LPS with large-sized HDL(2) strongly inhibited the effect of LPS to stimulate the luciferase production. When LPS was incubated with increased concentration of HDL(2), the LPS effect was decreased to a greater extent. Pre-incubation of LPS with HDL(2) before addition to the cells resulted in a significant decrease in the mRNA level of TNF-alpha. CONCLUSION: The largest HDL(2) has strong LPS-binding capacity and can inhibit the LPS induced TNF-alpha release in HepG2 cells; HDL(3) shows weak anti-LPS effect; small-sized prebeta(1)-HDL does not show anti-LPS effect.

Relationship between apolipoproteins and the alteration of HDL subclasses in hyperlipidemic subjects.

BACKGROUND: To elucidate the relationship between the apolipoproteins, especially apoA-I and the alteration of HDL subclasses in hyperlipidemic, HTC and HTG subjects. METHODS: ApoA-I contents of plasma HDL subclasses were quantitated by two-dimensional gel electrophoresis coupled with immunodetection in 233 normolipidemic subjects and 312 hyperlipidemic subjects (132 HTC and 180 HTG subjects). Making use of the mean +/-1 SD of apoA-I levels, we further subdivided normolipidemic, hyperlipidemic, HTC and HTG subjects into 3 subgroups, respectively. RESULTS: Subjects in the middle and low apoA-I subgroups had decreased HDL-C and apoA-I while increased TG, apoB100, apoCII, apoCIII and apoE concentrations. With the reduction of apoA-I concentrations, the apoA-I contents of all HDL subclasses decreased successively and significantly. The relative percentage of small-sized HDL increased significantly while those of large-sized HDL(2a), HDL(2b) decreased significantly in hyperlipidemic, especially in HTG group. Multiple liner regression result revealed that apoA-I was positively and significantly correlated with all HDL subclasses and apoA-I level influenced the distribution of HDL subclasses powerfully in hyperlipidemic subjects. CONCLUSIONS: Both the rate and efficiency of RCT might be weakened more seriously in hyperlipidemic, especially in HTG subjects with low apoA-I levels. ApoA-I level might be a powerful factor correlated with the distributions of HDL subclasses.

Relationship between apolipoprotein concentrations and HDL subclasses distribution.

Alterations in plasma apolipoproteins levels can influence the composition, content, and distribution of plasma lipoproteins that affect the risk of atherosclerosis. This study assessed the relationship between plasma apolipoproteins levels, mainly apoAI, and HDL subclass distribution. The contents of plasma HDL subclasses were determined by two-dimensional gel electrophoresis coupled with immunodetection in 545 Chinese subjects. Compared with a low apoAI group, the contents of all HDL subclasses increased significantly both in middle and high apoAI group, and the contents of large-sized HDL(2b) increased more significantly relative to those of small-sized prebeta(1)-HDL in a high apoAI group. When apoAI and HDL-C levels increased simultaneously, in comparison to a low apoAI along with HDL-C concentration group, a significant increase (116%) was shown in HDL2b but only a slight increase (26%) in prebeta1-HDL. In addition, Pearson correlation analysis revealed that apoAI levels were positively and significantly correlated with all HDL subclasses. Multiple liner regression demonstrated that the apoAI concentrations were the most powerful predictor for HDL subclass distribution. With the elevation of apoAI concentrations, the contents of all HDL subclasses increased successively and significantly, especially, an increase in large-sized HDL(2b). Further, when apoAI and HDL-C concentrations increased simultaneously, the shift to larger HDL size was more obvious. Which, in turn, indicated that HDL maturation might be enhanced and, the reverse cholesterol transport might be strengthened along with apoAI levels which might be a more powerful factor influencing the distribution of HDL subclasses.

Alterations of high-density lipoprotein subclasses in hypercholesterolemia and combined hyperlipidemia.

BACKGROUND: Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that effect atherosclerosis risk. Hypercholesterolemia and combined hyperlipidemia are common forms of atherogenic dyslipoproteinemia. This study evaluates the alterations of high-density lipoprotein (HDL) subclasses in hypercholesterolemic and combined hyperlipidemic subjects. METHODS: Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis in 242 normolipidemic subjects, 66 hypercholesterolemic subjects and 59 combined hyperlipidemic subjects. RESULTS: Compared with the normolipidemic subjects, apolipoprotein A-I contents of small-sized pre-beta1-HDL, HDL3c, HDL3b and HDL3a were significantly higher in both hypercholesterolemic subjects (p<.01, p<.05, p<.01 and p<.05, respectively) and combined hyperlipidemic subjects (p<.01, p<.05, p<.01 and p<.01, respectively). In contrast, apolipoprotein A-I contents of large-sized HDL2a and HDL2b were significantly lower in hypercholesterolemic subjects (p<.05 and p<.01, respectively) as well as combined hyperlipidemic subjects (p<.01 and p<.01, respectively). In addition, pre-beta1-HDL increased significantly (p<.05) while HDL2a and HDL2b decreased significantly (p<.05 and p<.01, respectively) in combined hyperlipidemic group versus hypercholesterolemic subjects. With the elevation of triglyceride levels, pre-beta1-HDL, and HDL3a increased successively, however, HDL2a and HDL2b decreased successively in subjects with total cholesterol levels greater than 240 mg/dl. CONCLUSIONS: The particle size of HDL shifted towards smaller size in hypercholesterolemic subjects, and that the shift was more prominent in combined hyperlipidemic subjects. The alternations mentioned above indicate that HDL maturation might be abnormal, and reverse cholesterol transport (RCT) might be weakened.

Relationship between total cholesterol/high-density lipoprotein cholesterol ratio, triglyceride/high-density lipoprotein cholesterol ratio, and high-density lipoprotein subclasses.

Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. This study evaluated the relationship between plasma total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, and HDL subclass distribution. The apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 442 Chinese subjects. The particle size of HDL shifted toward smaller size with the elevation of TC/HDL-C and TG/HDL-C ratios. The ratio of large-sized HDL(2b) to small-sized prebeta(1)-HDL (HDL(2b)/prebeta(1)-HDL) was about 4.7 in the subjects with TC/HDL-C of 3.3 or lower and TG/HDL-C of 2.5 or lower, whereas it was only approximately 1.1 in subjects with TC/HDL-C greater than 6 and TG/HDL-C greater than 5. Pearson correlation analysis revealed that the TC/HDL-C ratio was positively correlated with prebeta(1)-HDL and HDL(3a) but negatively correlated with HDL(2a) and HDL(2b), whereas the TC/HDL-C ratio was only inversely correlated with HDL(2b). The TC/HDL-C and TG/HDL-C ratios together may be a good indicator of HDL subclass distribution. When these 2 ratios increased simultaneously, the trend toward smaller HDL size was obvious, which, in turn, indicated that the maturation of HDL might be impeded and the reverse cholesterol transport might be weakened. In addition, the TG/HDL-C ratio might be a more powerful factor to influence the distribution of HDL subclasses.

Relationship between plasma HDL subclasses distribution and lipoprotein lipase gene HindIII polymorphism in hyperlipidemia.

BACKGROUND: Different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL directly influences the atherogenic process, and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Lipoprotein lipase (LPL) is an important enzyme for hydrolysis of triglyceride-rich lipoproteins, and its activity is positively correlated with the plasma HDL cholesterol level. LPL gene HindIII polymorphism has been found associated with variations in lipid levels, but the impact on HDL subclasses distribution is less clearly established. METHODS: The relative apolipoprotein (apo) A-I contents (% apoA-I) of plasma HDL subclasses were determined by two-dimensional gel electrophoresis coupled with immunodetection and LPL gene HindIII polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 173 hyperlipidemic and 155 normolipidemic subjects. RESULTS: The frequencies of 495TT genotype and allele T were the highest both in the hyperlipidemic and control groups. Compared with the control group, the frequency of 495TT genotype was higher, while the frequencies of 495TG and 495GG genotypes were significantly lower (P<0.05) in the hyperlipidemic group. Two-dimensional gel electrophoresis and immunodetection showed that HDL subclasses distribution was altered in hyperlipidemia, and had a general shift toward smaller size. Compared with the control group, the hyperlipidemic group had significantly higher relative apoA-I contents of prebeta1-HDL, prebeta2-HDL, HDL3b and HDL3a (P<0.05) and lower HDL2a and HDL2b levels (P<0.001). In the hyperlipidemic group, allele T carriers' frequency was higher than that in the control group (P<0.05), and the genotype of 495TT showed higher levels of plasma TG, apoB100, TG/HDL-C ratio, relative apoA-I contents of prebeta1-HDL, HDL3b and lower HDL2a, HDL2b compared with that of the 495GG genotype subgroup (P<0.05). In the control group, the genotype of 495TT had higher plasma TG, HDL3c and lower HDL2a compared with that of 495GG subgroup (P<0.05). CONCLUSIONS: The 495TT genotype of LPL gene HindIII polymorphism was associated with changes of HDL subclasses distribution in Chinese population with hyperlipidemia. The particle size of HDL shifted toward smaller, which, in turn, indicated that RCT might be weakened and HDL maturation might be abnormal in hyperlipidemic subjects with 495TT genotype.

Alterations of high-density lipoprotein subclasses in endogenous hypertriglyceridemia.

BACKGROUND: To investigate the alterations of high-density lipoprotein (HDL) subclasses in endogenous hypertriglyceridemic subjects. METHODS: Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis in 236 normolipidemic subjects (including 146 males and 90 females) and 176 endogenous hypertriglyceridemic subjects (including 103 males and 73 females). RESULTS: Apolipoprotein A-I contents of small-sized pre-beta1-HDL and HDL3a were significantly higher (P < .01 and P < .01, respectively), but those of large-sized HDL2a and HDL2b were significantly lower (P < .01 and P < .01, respectively) in hypertriglyceridemic subjects versus normolipidemic subjects. Moreover, with the elevation of triglyceride levels, small-sized pre-beta1-HDL and HDL3a increased successively; however, large-sized HDL2a and HDL2b decreased successively. Males had significantly higher apolipoprotein A-I contents of small-sized pre-beta1-HDL and HDL3b (P < .05 and P < .05, respectively), but lower contents of large-sized HDL2b (P < .01) than females in both normolipidemic and hypertriglyceridemic subjects. CONCLUSIONS: The particle size of HDL shifted toward smaller size in hypertriglyceridemic subjects, especially in male subjects. Of note, the shift was more obvious with the elevation of triglyceride levels. The changes mentioned above indicate that HDL maturation might be abnormal and reverse cholesterol transport might be weakened.

Relationship between plasma HDL subclasses distribution and apoA-I gene polymorphisms.

BACKGROUND: It is generally accepted that apolipoprotein (apo) A-I is the dominant structural apolipoprotein of HDL particles and different HDL subclasses have distinct but interrelated metabolic functions. HDL is known to directly affect the atherogenic process hence changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. METHODS: The ApoA-I contents (mg/l) of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection and apoA-I genotypes were assayed by PCR-RFLP in 307 Chinese subjects (169 males, 138 females). RESULTS: The G/G and C/C genotypes were the most frequent at -78 bp and +83 bp of apoA-I gene, respectively. There were no significant differences in the frequencies of rare A allele at -78 bp and rare T allele at +83 bp between males and females. Compared with the G/G carriers, G/A and A/A carriers had significantly higher plasma concentrations of TG, apoC-II, apoC-III, apoA-I contents of prebeta(1)-HDL, HDL(3a) and TG/HDL-C ratio. And in addition, A/A carriers had significantly lower apoA-I contents of HDL(2a) and HDL(2b). Females had increased plasma concentrations of apoA-I, HDL-C, apoA-I contents of HDL(2a) and HDL(2b) while decreased apoA-I contents of prebeta(1)-HDL, HDL(3b) and TG/HDL-C ratio as compared to males carrying the same genotype. No significant differences were demonstrated on the concentrations of plasma lipids, lipoproteins, apolipoproteins and apoA-I contents of plasma HDL subclasses between the C/C and C/T subjects. CONCLUSION: The G/A polymorphism at -78 bp of apoA-I gene was associated with changes of HDL subclasses distribution. There was a general shift towards smaller-sized HDL, which, in turn, indicated that reverse cholesterol transport (RCT) might be weakened and HDL maturation might be abnormal in the subjects with G/A mutation.