Low density lipoprotein (LDL), atherosclerosis and antioxidants

A crucial and causative role in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low density lipoprotein (LDL). The oxidation of LDL involves released free radical driven lipid peroxidation. Several lines of evidence support the role of oxidized LDL in atherogenesis. Epidemiologic studies have demonstrated an association between an increased intake of dietary antioxidant vitamins, such as vitamin E and vitamin C and reduced morbidity and mortality from coronary artery diseases. It is thus hypothesized that dietary antioxidants may help prevent the development and progression of atherosclerosis. The oxidation of LDL has been shown to be reduced by antioxidants, and, in animal models, improved antioxidants may offer possibilities for the prevention of atherosclerosis. The results of several on going long randomized intervention trials will provide valuahle information on the efficacy and safety of improved antioxidants in the prevention of atherosclerosis. This review a evaluates current literature involving antioxidants and vascular disease, with a particular focus on the potential mechanisms.     

Protective effects of vitamin E against hypercholesterolemia-induced age-related diseases

Hypercholesterolemia is a major risk factor for age-related diseases such as atherosclerosis and Alzheimer’s disease (AD). Changes in human plasma cholesterol levels results from the interaction between multiple genetic and environmental factors. The accumulation of excess cholesterol in blood vessels leads to atherosclerosis. Many studies on this field show that differential expression of oxidative stress-related proteins, lipid metabolism-related enzymes, and receptors response to atherogenic diet. Additionally, excess brain cholesterol has been associated with increased formation and deposition of amyloid-β peptide from amyloid precursor protein which may contribute to the risk and pathogenesis of AD. To consider genetically, more than 50 genes have been reported to influence the risk of late-onset AD. Some of these genes might be also important in cholesterol metabolism and transport. Epidemiological studies have shown an association between high intake and high serum concentrations of antioxidant vitamins like vitamin E and lower rates of ischemic heart diseases. It has been known that vitamin E also inhibits smooth muscle cell proliferation by non-antioxidant mechanism. On the basis of the previous results, vitamin E has been accepted as an important protective factor against hypercholesterolemia-induced age-related diseases.     

Molecular mechanisms of cholesterol or homocysteine effect in the development of atherosclerosis: Role of vitamin E

The development of atherosclerosis is a multifactorial process in which both elevated plasma cholesterol levels and proliferation of smooth muscle cells play a central role. Numerous studies have suggested the involvement of oxidative processes in the pathogenesis of atherosclerosis and especially of oxidized low density lipoprotein. Some epidemiological studies have shown an association between high dietary intake and high serum concentrations of vitamin E and lower rates of ischemic heart disease. Cell culture studies have shown that alpha-tocopherol brings about inhibition of smooth muscle cell proliferation. This takes place via inhibition of protein kinase C activity. alpha-Tocopherol also inhibits low density lipoprotein induced smooth muscle cell proliferation and protein kinase C activity. The following animal studies showed that vitamin E protects development of cholesterol induced atherosclerosis by inhibiting protein kinase C activity in smooth muscle cells in vivo. Elevated plasma levels of homocysteine have been identified as an important and independent risk factor for cerebral, coronary and peripheral atherosclerosis. However the mechanisms by which homocysteine promotes atherosclerotic plaque formation are not clearly defined. Earlier reports have been suggested that homocysteine exert its effect via H2O2 produced during its metabolism. To evaluate the contribution of homocysteine in the pathogenesis of vascular diseases, we examined whether the homocysteine effect on vascular smooth muscle cell growth is mediated by H2O2. We show that homocysteine induces DNA synthesis and proliferation of vascular smooth muscle cells in the presence of peroxide scavenging enzyme, catalase. Our data suggest that homocysteine induces smooth muscle cell growth through the activation of an H2O2 independent pathway and accelerate the progression of atherosclerosis. The results indicate a cellular mechanism for the atherogenicity of cholesterol or homocysteine and protective role of vitamin E in the development of atherosclerosis.     

Correlation between the extent of coronary atherosclerosis and lipid profile

Increased concentration of low density lipoprotein (LDL) cholesterol or decreased level of high density lipoprotein (HDL) cholesterol are important risk factors for coronary atherosclerosis. However, an independent association of triglycerides (TG) with atherosclerosis is uncertain.The aim of this prospective study was to evaluate the relationship between serum lipid levels and the extent of coronary atherosclerosis in patients with suspected coronary artery disease (CAD) and no previous myocardial infarction who were not treated with lipids lowering therapy or low-lipid diet.The study was conducted in 141 patients (53.6 ± 7.8 years old; 32 female) who underwent a routine coronary angiography for CAD diagnosis. A modified angiographic Gensini Score (GS) was used to reflect the extent of coronary atherosclerosis. Fasting serum lipid concentrations were determined using cholesterol esterase/peroxidase (CHOD/PAP) enzymatic method for total cholesterol and its fractions and lipase glycerol kinase (GPO/PAP) enzymatic method TG evaluation. The association of Gensini Score with variables characterising lipid profile was analysed with the use of Pearson correlation (r co-efficient; p value).GS was positively correlated with total cholesterol (r = 0.404; p < 0.001), LDL cholesterol (r = 0.484; p < 0.001) and TG (r = 0.235; p = 0.005). There was a negative correlation between Gensini Score and HDL cholesterol (r = –0.396; p < 0.001).In angina pectoris patients with no previous myocardial infarction, the extent of coronary atherosclerosis is positively correlated with pro-atherogenic lipids, i.e. total cholesterol, LDL cholesterol and TG and negatively correlated with antiatherogenic HDL cholesterol.     

Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement.

The 'oxidation theory' of atherosclerosis proposes that oxidation of low density lipoprotein (LDL) contributes to atherogenesis. Although little direct evidence for a causative role of 'oxidized LDL' in atherogenesis exists, several studies show that, in vitro, oxidized LDL exhibits potentially proatherogenic activities and lipoproteins isolated from atherosclerotic lesions are oxidized. As a consequence, the molecular mechanisms of LDL oxidation and the actions of alpha-tocopherol (alpha-TOH, vitamin E), the major lipid-soluble lipoprotein antioxidant, have been studied in detail. Based on the known antioxidant action of alpha-TOH and epidemiological evidence, vitamin E is generally considered to be beneficial in coronary artery disease. However, intervention studies overall show a null effect of vitamin E on atherosclerosis. This confounding outcome can be rationalized by the recently discovered diverse role for alpha-TOH in lipoprotein oxidation; that is, alpha-TOH displays neutral, anti-, or, indeed, pro-oxidant activity under various conditions. This review describes the latter, novel action of alpha-TOH, termed tocopherol-mediated peroxidation, and discusses the benefits of vitamin E supplementation alone or together with other antioxidants that work in concert with alpha-TOH in ameliorating lipoprotein lipid peroxidation in the artery wall and, hence, atherosclerosis.     

Total cholesterol,low density lipoprotein cholesterol,and high density lipoprotein cholesterol and coronary heart disease in Scotland.

OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION--Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes.     

Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.

To examine the association between cigarette smoking in adults and serum lipid and lipoprotein concentrations the results of 54 published studies were analysed. Overall, smokers had significantly higher serum concentrations of cholesterol (3.0%), triglycerides (9.1%), very low density lipoprotein cholesterol (10.4%), and low density lipoprotein cholesterol (1.7%) and lower serum concentrations of high density lipoprotein cholesterol (-5.7%) and apolipoprotein AI (-4.2%) compared with nonsmokers. Among non-smokers and light, moderate, and heavy smokers a significant dose response effect was present for cholesterol (0, 1.8, 4.3, and 4.5% respectively), triglycerides (0, 10.7, 11.5, and 18.0%), very low density lipoprotein cholesterol (0, 7.2, 44.4, and 39.0%), low density lipoprotein cholesterol (0, -1.1, 1.4, and 11.0%), high density lipoprotein cholesterol (0, -4.6, -6.3, and -8.9%), and apolipoprotein AI (0, -3.7 and -5.7% in non-smokers and light and heavy smokers). These dose response effects may provide new evidence for a causal relation between exposure to cigarette smoke and changes in serum lipid and lipoprotein concentrations whether as a direct result of physiological changes or of dietary changes induced by smoking. Adequate prospective data to estimate the excess risk of coronary artery disease existed only for cholesterol concentration. When that information was combined with data from the present study, and given that smokers as a group face an average overall excess risk of coronary artery disease of 70%, it was estimated that the observed increased serum cholesterol concentration in smokers may account for at least 9% of that excess risk. Furthermore, the dose response effect of smoking on serum cholesterol concentration suggests a gradient of increased absolute risk of coronary artery disease between light and heavy smokers.     

Serum vitamins E, A and lipid peroxidation levels in Kurichias, an Indian tribal population.

Serum vitamins E, A, lipid peroxides, prevalence of dislipidemia, hypertension, obesity and smoking habits were assessed in a volunteer sample of 310 (175 males + 135 females) Kurichias, a tribal population of Kerala, India, who are enjoying longevity relatively free from age associated chronic problems. The mean serum levels of vitamins E and A were higher and lipid peroxides were lower with comparable ages of Indian and Western studies. The prevalence (age standardized to the world population of Segi 95% CI) was obesity 2.87 (1.22-4.53), central obesity 3.71 (2.27-5.15), hypertension 2.70 (1.92-3.48), hypercholesterolemia 0.71 (0.66-0.76), hypertriglyceridemia 2.60 (1.18-4.02) and low high density lipoprotein cholesterol 1.24 (1.07-1.42). Significant negative correlation was observed between vitamins and lipid peroxides. Serum cholesterol and triglycerides showed significant positive correlation with antioxidant vitamins and lipid peroxides. Blood pressure found positive correlation with lipid peroxides and no correlation with vitamins except systolic blood pressure having negative relation with vitamin A. Age showed negative correlation with vitamins and positive correlation with lipid peroxides, whereas lipid peroxides showed positive correlation with obesity only. In multivariate regression analysis serum cholesterol and old age groups were significant predictors of serum antioxidant vitamins and lipid peroxides. The higher levels of antioxidant vitamins, lower levels of lipid peroxides as well as low prevalence of CHD risk factors in Kurichias when compared to other populations suggest that antioxidants or increased intake of foods rich in antioxidants play a key role in their health and longevity.     

Diabetic dyslipidemia and exercise alter the plasma low‐density lipoproteome in Yucatan pigs

Although low‐density lipoprotein (LDL) plays a predominant role in atherogenesis, the low‐density lipoproteome has not been fully characterized. Moreover, alterations from a Western diet, diabetes, and physical inactivity on this proteome have yet to be determined. Accordingly, relative quantification was determined in LDL proteins from male Yucatan diabetic dyslipidemic (DD) swine in the early stages of atherosclerosis compared to healthy control (C) and non‐diabetic hyperlipidemic (H) swine. Importantly, coronary vascular dysfunction was prevented by aerobic exercise training in these animals (DDX) without altering total LDL concentration. Using 2‐DE, Western blot, label‐free quantitative MS, and selected reaction monitoring, alterations in the abundance of apolipoproteins A‐I, B, C‐III, D, E, and J and noncovalently associated proteins were determined in LDL isolated using fast protein liquid chromatography. At least 28 unique proteins, many of which were novel, were identified with high confidence. An apolipoprotein E isoform demonstrated stronger correlation to disease (percent of coronary artery segments with intimal thickening) than some traditional risk factors (total cholesterol, LDL cholesterol, and LDL/HDL cholesterol). Taken together, this work identifies new possible biomarkers, potential therapeutic targets for atherosclerosis, and generates new hypotheses regarding the role of LDL in atherogenesis.     

女性冠心病患者的危险因素分析及与冠脉病变严重程度的关系

目的:了解女性冠心病患者的危险因素及与冠脉病变严重程度的关系。方法:随机选取本院2012年至2014年心血管科住院治疗的疑似冠心病女性患者150例,经冠脉造影确诊冠心病患者105例,非冠心病患者45例。对患者的临床资料和冠脉病变严重程度进行单因素和多因素分析。结果:冠心病患者高血压与糖尿病百分比、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)及纤维蛋白原水平均高于非冠心病患者,而高密度脂蛋白(HDL-C)和血红蛋白水平均低于非冠心病患者(P0.05);年龄、高血压与糖尿病百分比、血脂上升百分比(高TC、高TG、低HDL-C、高LDL-C)、高尿酸百分比和纤维蛋白原水平均随冠状动脉病变支数及Gensini积分的增加而增加(P0.05);多因素分析发现女性冠心病的影响因素分别为高LDL-C、糖尿病、低HDL-C、TG和高血压,其中高LDL-C的影响最为显著(P0.05)。结论:高血压、糖尿病史、血脂水平为女性冠心病的影响因素,其中高LDL-C的影响最显著,各影响因素均与冠脉病变程度紧密相关。     

Psychosocial and reproductive influences on plasma lipids, lipoproteins, and atherosclerosis in nonhuman primates

Until recently, research in experimental atherosclerosis focused primarily on nutritional influences on plasma lipids, lipoproteins, and atherosclerosis. We review here the results of recent studies of independent and interactive influences of psychosocial and reproductive influences on atherosclerosis in nonhuman primates. These studies have produced evidence that, as in human beings, individuals with certain personality characteristics who are frequently faced with stressful or challenging situations are at increased risk of coronary artery disease. Preliminary evidence suggests that this relationship may be mediated, in part, by heightened sympathetic arousal, i.e., cardiovascular hyperresponsiveness, to the environmental challenge. Also, as in human beings, evidence has been produced that certain negative behavioral and psychosocial variables can have a significant independent influence on plasma lipids. As regards reproductive influences, the cynomolgus macaque seems to share with premenopausal white women a relative protection against coronary artery atherosclerosis. This "female protection" against diet-induced atherosclerosis is abolished by ovariectomy, which also results in increased total plasma and low density lipoprotein (LDL) cholesterol concentrations. Subordinate social status also seems to abolish female protection in some individuals. Preliminary evidence suggests that subordinate females most liable to this loss of protection are those with apparent stress-induced chronic ovarian endocrine dysfunction, which, in turn, is associated with increased plasma LDL cholesterol and decreased plasma high density lipoprotein (HDL) cholesterol concentrations.     

Sialic acid and oxidizability of lipid and proteins and antioxidant status in patients with coronary artery disease

The aim of this study was to investigate the possible relationship between serum total sialic acid (TSA) concentration, recently shown to be a cardiovascular risk factor, and lipid and protein oxidation and antioxidant status and the severity of coronary artery disease (CAD) according to the obstructive vessel number in patients. The study was carried out on a total of 200 patients (142 men and 58 women) who were hospitalized for elective coronary angiographic evaluation with complaint of typical angina pectoris. According to the results of angiography, 150 patients had angiographically proven CAD (CAD group) and 50 patients had a history suggestive of angina pectoris but normal coronary angiograms (control group). The CAD group was further divided into single-, double- and triple-vessel disease groups according to the number of vessels involved. Lipid parameters were determined by routine laboratory methods. Plasma malondialdehyde (MDA) and vitamin E concentrations were determined by high-performance liquid chromatography. TSA and other oxidant and antioxidant parameters were studied spectrophotometrically. Our results demonstrated significant increases both in TSA levels and in indicators of oxidative stress in the patients with CAD compared with the controls. However, antioxidant parameters were decreased in the patients with CAD. We found strong positive correlations between TSA and plasma MDA, Delta-MDA which represents the degree of oxidative modification of apolipoprotein B-containing lipoproteins, serum protein carbonyls and apolipoprotein B and weak correlations between TSA and low density lipoprotein cholesterol, triacylglycerol, paraoxonase, glutathione peroxidase (GPx), vitamin C and vitamin E. In conclusion, TSA is related to markers of lipid and protein oxidation, paraoxonase and GPx activities, vitamin C and E levels and the severity of CAD.     

综述: HDL蛋白质组分临床研究新进展

高密度脂蛋白胆固醇(HDL-C)水平与冠心病风险呈负相关,低HDL-C水平增加心血管疾病风险,是心血管疾病的独立危险因素．然而升高HDL-C水平的药物治疗并没有明显的临床获益,没有起到降低心血管疾病风险的预期效果,因此高密度脂蛋白(HDL)功能比HDL-C水平更好地预测心血管事件的发生．HDL是蛋白质含量最高的脂蛋白,由于蛋白质组学技术的进步,越来越多的HDL蛋白质成分被发现,除了传统的载脂蛋白、酶类,还包括脂质转移蛋白、急性期反应蛋白、补体成分、蛋白酶抑制剂,HDL的功能也从脂质转运扩展到感染免疫、急性期反应、补体激活、离子结合等,不仅参与动脉粥样硬化的发生发展,在终末期肾病、糖尿病等高心血管风险疾病中也发挥重要作用．本文就HDL蛋白质成分、功能及在冠心病和高心血管风险疾病中的作用做一综述．     

Oxidation of low-density lipoprotein in atherosclerosis from basic biochemistry to clinical studies

Although it has been known for long time that atherosclerosis is associated with lipid deposition, only recently it has been accepted that the plasmatic concentration of cholesterol, especially LDL cholesterol, is a risk factor for atherosclerosis. However, chemically modified LDL, but not native LDL, is able to induce the formation of foam cells, the hallmark of atherosclerosis. LDL oxidation is likely to be the most important form of LDL modification in humans. In biochemical terms, LDL oxidation is a free radical driven chain reaction where polyunsaturated fatty acids are converted to lipid peroxides, which easily decompose to many products, including biologically active aldehydes. The assay of LDL oxidation in biological fluids is problematic; direct assays detect a product of LDL oxidation whereas indirect assays give an indicator of LDL oxidation susceptibility. In general, epidemiological studies support the concept that the level of plasmatic lipophilic antioxidants, tocopherols and carotenoids, is low in populations at increased risk for atherosclerosis. However, clinical trials based on vitamin E as antioxidant showed inconclusive results, suggesting that supplementation with vitamin E is not generically recommended for atherosclerotic patients. These results, however, do not contradict that oxidation of lipoprotein is involved in atherosclerosis; rather, this negative outcome raises a number of considerations such as the need for a reliable marker of lipoprotein oxidation in plasma and a more complete information about the physiological triggers of lipoprotein oxidation.     

Thrombopoietin upregulates nucleolin mRNA and protein in thrombopoietin-dependent megakaryocytic cell line,UT-7/TPO

In a randomized, double-blind, controlled trial, the effects of oral treatment with coenzyme Q10 (CoQ10, 120 mg/day), a bioenergetic and antioxidant cytoprotective agent, were compared for 1 year, on the risk factors of atherosclerosis, in 73 (CoQ, group A) and 71 (B vitamin group B) patients after acute myocardial infarction (AMI). After 1 year, total cardiac events (24.6 vs. 45.0%, p < 0.02) including non-fatal infarction (13.7 vs. 25.3%, p < 0.05) and cardiac deaths were significantly lower in the intervention group compared to control group. The extent of cardiac disease, elevation in cardiac enzymes, left ventricular enlargement, previous coronary artery disease and elapsed time from symptom onset to infarction at entry to study showed no significant differences between the two groups. Plasma level of vitamin E (32.4 ± 4.3 vs. 22.1 ± 3.6 umol/L) and high density lipoprotein cholesterol (1.26 ± 0.43 vs. 1.12 ± 0.32 mmol/L) showed significant (p < 0.05) increase whereas thiobarbituric acid reactive substances, malondialdehyde (1.9 + 0.31 vs. 3.1 + 0.32 pmol/L) and diene conjugates showed significant reduction respectively in the CoQ group compared to control group. Approximately half of the patients in each group (n = 36 vs. 31) were receiving lovastatin (10 mg/day) and both groups had a significant reduction in total and low density lipoprotein cholesterol compared to baseline levels. It is possible that treatment with CoQ10 in patients with recent MI may be beneficial in patients with high risk of atherothrombosis, despite optimal lipid lowering therapy during a follow-up of 1 year. Adverse effect of treatments showed that fatigue (40.8 vs. 6.8%, p < 0.01) was more common in the control group than CoQ group.     

Obesity-related changes in high-density lipoprotein metabolism

Obesity is associated with a 3-or-more-fold increase in the risk of fatal and nonfatal myocardial infarction (1,2,3,4,5,6). The American Heart Association has reclassified obesity as a major, modifiable risk factor for coronary heart disease (7). The increased prevalence of premature coronary heart disease in obesity is attributed to multiple factors (8,9,10). A principal contributor to this serious morbidity is the alterations in plasma lipid and lipoprotein levels. The dyslipidemia of obesity is commonly manifested as high plasma triglyceride levels, low high-density lipoprotein cholesterol (HDLc), and normal low-density lipoprotein cholesterol (LDLc) with preponderance of small dense LDL particles (7,8,9,10). However, there is a considerable heterogeneity of plasma lipid profile in overweight and obese people. The precise cause of this heterogeneity is not entirely clear but has been partly attributed to the degree of visceral adiposity and insulin resistance. The emergence of glucose intolerance or a genetic predisposition to familial combined hyperlipidemia will further modify the plasma lipid phenotype in obese people (11,12,13,14,15).     

Plasma lipid transfer proteins

PURPOSE OF REVIEW: Plasma cholesteryl ester transfer protein and phospholipid transfer protein are involved in lipoprotein metabolism. Conceivably, manipulation of either transfer protein could impact atherosclerosis and other lipid-driven diseases. RECENT FINDINGS: Cholesteryl ester transfer protein mediates direct HDL cholesteryl ester delivery to the liver cells; adipose tissue-specific overexpression of cholesteryl ester transfer protein in mice reduces the plasma HDL cholesterol concentration and adipocyte size; cholesteryl ester transfer protein TaqIB polymorphism is associated with HDL cholesterol plasma levels and the risk of coronary heart disease. In apolipoprotein B transgenic mice, phospholipid transfer protein deficiency enhances reactive oxygen species-dependent degradation of newly synthesized apolipoprotein B via a post-endoplasmic reticulum process, as well as improving the antiinflammatory properties of HDL in mice. Activity of this transfer protein in cerebrospinal fluid of patients with Alzheimer's disease is profoundly decreased and exogenous phospholipid transfer protein induces apolipoprotein E secretion by primary human astrocytes in vitro. SUMMARY: Understanding the relationship between lipid transfer proteins and lipoprotein metabolism is expected to be an important frontier in the search for a therapy for atherosclerosis.     

Cholesterol metabolism and transport in the pathogenesis of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the ?4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins – drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.     

HDL-C及其亚型与冠心病患者预后关系的相关性研究

目的:探讨高密度脂蛋白胆固醇(HDL-C)及其亚型与冠心病患者预后的关系。方法:选取2012年6月~2015年12月在我院检查的371例疑似冠心病患者为研究对象,其中确诊为冠心病患者274例为观察组,冠状动脉检查正常者97例为对照组。对两组患者的血脂指标进行检测,同时分析各终点事件与血脂各指标之间的相关性,并采用COX回归分析探讨HDL-C及其亚型与冠心病患者预后的关系。结果:与正常组比较,冠心病患者总胆固醇、低密度脂蛋白胆固醇等指标显著升高,而高密度脂蛋白胆固醇及其亚型HDL2-C显著降低。这种改变随冠状动脉病变支数的增加而更加显著。COX回归分析显示HDL2-C亚型与患者心源性死亡的发生风险存在一定的相关性。结论:HDL2-C亚型与冠心病的发生、发展,患者病变程度存在显著的相关性,可以用作对冠心病患者病情程度和终点事件预测的重要参考指标。     

Genetic variations of cholesterol ester transfer protein gene in Koreans.

An absence of cholesterol ester transfer protein (CETP, protein; CETP, gene) results in an increase of the apolipoprotein AI levels and a decrease in the low density lipoprotein (LDL) levels. Thus, the CETP polymorphism is important in the assessment of risk of atherosclerosis. This study was conducted to elucidate the genotype distributions of the CETP polymorphism and association with plasma lipid levels in Koreans. The genotypes of the TaqI A and B polymorphic loci were associated with plasma triglyceride levels in the control and coronary artery disease (CAD) groups. There was linkage disequilibrium between TaqI A and B loci in the control group (chi2 = 5.58, p < 0.05). Association studies of the CETP polymorphism have been carried out mainly with Caucasian populations; however, the results have not been consistent among different populations. A possible explanation for this diversity among populations may be differences in genetic backgrounds, which may be more important than environmental factors. We discuss the reasons for the incompatibility of the CETP polymorphism among populations.