脑梗死患者颈动脉粥样硬化的相关因素分析

目的:探讨脑梗死患者颈动脉粥样硬化的危险因素。方法:选取148例脑梗死患者作为实验组和同期住院的80例非脑梗死疾病患者为对照组,检测并比较各组年龄、吸烟、血压、饮酒、糖尿病、血脂、同型半胱氨酸和磷脂酶A2等指标,然后进行卡方检验、相关性和Logistic回归分析。结果:实验组颈动脉粥样硬化检出率为82.43%,对照组为12.5%,其差异具有统计学意义(P0.05)。高龄、吸烟、高血压、高血脂、高同型半胱氨酸血症、高磷脂酶A2(LP-PLA2)血症是经动脉粥样硬化的危险因素,且血浆同型半胱氨酸水平、LP-PLA2水平、血压与颈动脉斑块稳定性有关(P0.05)。结论:颈动脉粥样硬化是脑梗死的病理基础,与高龄、吸烟、高血压、高血脂、高同型半胱氨酸血症、高磷脂酶A2(LP-PLA2)血症有关,对高同型半胱氨酸血症、LP-PLA2和高血压患者要关注其斑块的稳定性。     

Blood ethanol levels in sober alcohol users seen in an emergency room

During the course of two years, 76 representative subjects seen in a community hospital emergency room who admitted to having recently used alcohol while still appearing sober had their blood alcohol levels measured to determine the levels of blood alcohol present in ambulatory sober alcohol users. As a group the mean blood alcohol level obtained in those who had measurable levels was 268 ± 10 mg/dl mean ± SEM). More men (47) than women (18) admitted to having used ethanol and had measurable blood ethanol levels and therefore were studied. Moreover, the mean blood alcohol level in the men studied was arithmetically greater (272 ± 13 mg/d1) than that present in the women (260 ± 13mg/d1). The range of alcohol levels seen in the two sexes, however, were quite similar. Using a blood alcohol level > 200 mg/dl in a clinically “non-intoxicated” individual as the cut-off level for defining one as a suspect chronic alcohol user, our data would suggest that such individuals not uncommonly have blood alcohol levels as high as 290 ± 9 mg/dl.     

Hypolipidemic and antioxidant effects of Morus alba L. (Egyptian mulberry) root bark fractions supplementation in cholesterol-fed rats

The 70% alcohol extract of the Egyptian Morus alba L. root bark was fractionated over cellulose CC eluted with water, 50% methanol and finally with 100% methanol to yield 3 fractions (MRBF-1, MRBF-2 and MRBF-3), respectively. In continuation of chromatographic purification of 70% alcohol extract fractions of the Egyptian M. alba L. root bark, 4 compounds namely: mulberroside A, 5,7,2'-trihydroxyflavanone-4'-O-beta-D-glucoside and albanols A and B were isolated from MRBF-2 for the first time from the Egyptian plant. Experimentally induced atherosclerosis was produced by feeding rats a diet enriched in coconut oil (25% by weight) and cholesterol (2% by weight) for 21 days. Then, hypercholesterolemic rats were orally administered (MRBF-1, MRBF-2 and MRBF-3 fractions) in a dose of 500 mg kg(-1) day(-1) for 15 successive days, in order to evaluate their expected hypocholesterolemic activity. Lipid profile parameters such as plasma total cholesterol, LDL-C, VLDL-C, LDL:HDL ratio and triglycerides, as well as plasma and liver lipid peroxides and glutathione-S-transferase enzyme levels, serum paraoxonase enzyme level, LDL oxidation, LDL aggregation and LDL retention, were measured. Plasma and liver glutathione-S-transferase enzyme levels were unaffected in all studied groups. The results revealed that the administration of (MRBF-2 and/or MRBF-3) fractions resulted in alleviation of atherosclerotic state. Administration of MRBF-3 significantly retained plasma and liver peroxides towards their normal levels, and also, produced significant increase in resistance towards major atherogenic modifications; namely LDL oxidation, LDL aggregation and LDL retention by 44%, 30%, and 33%, respectively. Thus, it can be concluded that the consumption of MRBF-2 and (MRBF-3, in some extent) fractions of M. alba L. root bark 70% alcohol extract may act as a potent hypocholesterolemic nutrient and powerful antioxidant via the inhibition of LDL atherogenic modifications and lipid peroxides formation in hypercholesterolemic rats.     

Antiatherogenic potential of red wine: clinician update

Complications of atherosclerosis remain the leading cause of morbidity and mortality in industrialized countries. Epidemiological studies have repeatedly demonstrated that moderate alcohol intake has a beneficial effect on cardiovascular disease. The purpose of this review is to examine the epidemiological and biological evidence supporting the intake of red wine as a means of reducing atherosclerosis. On the basis of epidemiological studies, moderate intake of alcoholic beverages, including red wine, reduces the risk of cardiovascular, cerebrovascular, and peripheral vascular disease in populations. In addition to the favorable biological effects of alcohol on the lipid profile, on hemostatic factors, and in reducing insulin resistance, the phenolic compounds in red wine appear to interfere with the molecular processes underlying the initiation, progression, and rupture of atherosclerotic plaques. Whether red wine is more beneficial than other types of alcohol remains unclear. Definitive data from a large-scale, randomized clinical end-point trial of red wine intake would be required before physicians can advise patients to use wine as part of preventative or medical therapies.     

NO-1886 upregulates ATP binding cassette transporter A1 and inhibits diet-induced atherosclerosis in Chinese Bama minipigs

It is widely believed that high density lipoprotein-cholesterol (HDL-C) functions to transport cholesterol from peripheral cells to the liver by reverse cholesterol transport (RCT), a pathway that may protect against atherosclerosis by clearing excess cholesterol from arterial cells. A cellular ATP binding cassette transporter called ABCA1 mediates the first step of RCT. NO-1886 has been proven to be highly effective at increasing HDL-C and reducing atherosclerosis. However, the mechanism of atherosclerosis inhibition for NO-1886 is not fully understood. In this study, the effects of NO-1886 on ABCA1 were investigated in high-fat/high-sucrose/high-cholesterol-fed Chinese Bama minipigs. Administration of NO-1886 (0.1 g/kg body weight/day) in the diet for 5 months significantly reduced atherosclerosis lesions and significantly increased plasma HDL-C and apolipoprotein A-I levels. The mRNA and protein levels of ABCA1 in the liver, retroperitoneal adipose tissue, and aorta were increased by NO-1886 as well. Multivariate linear regression analysis showed that the levels of LPL in plasma and the levels of ABCA1 in aorta were independently associated with the atherosclerotic lesion area. In addition, NO-1886 upregulated liver X receptor alpha and affected the expression of scavenger receptor class B type I in the liver. These results demonstrate that the mechanism of atherosclerosis inhibition for NO-1886 is associated with its effect on ABCA1.     

Alcohol, wine and platelet function

Epidemiological studies have demonstrated an inverse correlation between moderate wine and alcohol consumption and morbidity and mortality from coronary heart disease. The protective effect has been associated with an increase in the plasma level of HDL cholesterol, as it is well recognized that plasma HDL is inversely correlated with CHD. In addition, it has become evident that blood platelets contribute to the rate of development of atherosclerosis and CHD through several mechanisms. In recent studies it has been shown that the level of HDL cholesterol can explain only 50% of the protective effect of alcoholic beverages; the other 50% may be partly related to a decrease in platelet activity. This anti-platelet activity of wine is explained by ethanol but also by the polyphenolic components with which red wines are richly endowed. Several studies carried out on humans and animals have shown that wine phenolics could exert their effects by reducing prostanoid synthesis from arachidonate. In addition, it has been suggested that wine phenolics could reduce platelet activity mediated by nitric oxide. Moreover, wine phenolics increase vitamin E levels while decreasing the oxidation of platelets submitted to oxidative stress. However, a rebound phenomenon of hyperaggregability is observed after an acute alcohol consumption which is not observed with wine consumption. This protection afforded by wine has been duplicated in animals with grape phenolics added to alcohol. The rebound phenomenon may explain ischemic strokes or sudden deaths known to occur after episodes of drunkenness. It appears that wine, and wine phenolics in particular, could have a more significant inhibitory effect on platelet aggregation and could explain, in part, the hypothesis that red wine is more protective against atherosclerosis and coronary heart disease.     

Serum levels of the MCP-1 chemokine in patients with ischemic stroke and myocardial infarction

Chemokine-driven migration of inflammatory cells has been implicated in pathogenesis of atherosclerosis-associated conditions such as ischemic stroke and myocardial infarction. In this study, a candidate chemokine, monocyte chemoattractant protein (MCP)-1, was investigated in patients with both aforementioned manifestations of atheroslerotic inflammation. MCP-1 levels in serum were determined by ELISA in 40 healthy, control subjects (C), 40 patients with ischemic stroke (IS), and in 64 patients with myocardial infarction (MI). Statistical analysis utilised Mann-Whitney test, Fisher's exact test, and Spearman's rank correlation (P < .05). In comparison to control subjects (C; median/interquartile range: 239/126 pg/mL), MCP-1 serum levels were increased in both investigated patient cohorts (IS: 384/370, P < .001; MI: 360/200, P < .002). There was a substantial variability of MCP-1 serum levels, especially in the IS group. No relationship was observed between chemokine levels and atherosclerosis risk factors (hypertension, diabetes, smoking, and alcohol consumption), and MCP-1 was also not related to age or gender. Elevation of MCP-1 in circulation of patients with atherosclerosis-associated complications implicates this CC chemokine ligand (CCL)2 in inflammatory processes, which contribute to pathogenesis of myocardial infarction and ischemic stroke. Further investigations, including patient stratification, are however necessary to evaluate if MCP-1 can be utilised for clinical management of patients with these diseases.     

Association between hemoglobin A1c and carotid atherosclerosis in rural community-dwelling elderly Japanese men

Background

Recent studies have reported an association between both higher and lower levels of hemoglobin A1c (HbA1c) and higher mortality of diabetes patients. Like diabetes, carotid atherosclerosis is a well known lifestyle-related disease. However, no studies have yet reported an association between HbA1c levels and carotid atherosclerosis.

Methods

We conducted a cross-sectional study of 1,150 Japanese elderly men aged ≥60 years who were undergoing general health checkups. Carotid atherosclerosis was defined as a carotid intima-media thickness (CIMT) ≥1.1 mm. Since body mass index (BMI) is regarded as a cardiovascular risk factor that exerts a strong influence on both HbA1c levels and carotid atherosclerosis, we performed a stratified analysis of this risk based on BMI.

Results

Using the intermediate HbA1c quintile as a reference group, the groups in the lowest HbA1c quintiles showed a significantly higher risk of carotid atherosclerosis in patients with low BMI (≤23 kg/m²) vs. no increased risk in those with high BMI (>23 kg/m²). The association of HbA1c with carotid atherosclerosis became slightly stronger when these analyses were limited to subjects who were not taking glucose-lowering medications or medications for hyperlipidemia and cardiovascular disease. After adjusting for classical cardiovascular risk factors, adjusted odds ratios (ORs) for carotid atherosclerosis were 1.36 (0.84 to 2.20) for total subjects, 2.29 (1.12 to 4.66) for low-BMI groups, and 0.68 (0.33 to 1.41) for high-BMI groups.

Conclusions

Lower HbA1c level is a significant risk factor for carotid atherosclerosis in rural community-dwelling elderly Japanese men with low, but not high BMI, particularly in those not taking glucose-lowering medication.     

Overexpression of Prdx6 reduces H2O2 but does not prevent diet-induced atherosclerosis in the aortic root

The mammalian 1-Cys peroxiredoxin (Prdx6) is a unique member of the peroxiredoxin family of proteins capable of protecting cells from metal-catalyzed oxidative damage. We recently identified Prdx6 as a candidate for the quantitative trait locus Ath1, a gene responsible for a difference in diet-induced atherosclerosis susceptibility in mice. To investigate the role of Prdx6 in atherosclerosis, we generated transgenic mice that overexpress the Prdx6 allele from the Ath1-resistant 129/SvJ strain on an Ath1-susceptible C57BL/6J background. These mice expressed significantly elevated levels of Prdx6 mRNA and protein in multiple tissues including liver, aorta, and peritoneal macrophages, which accumulated significantly lower levels of hydrogen peroxide, revealing an enhanced antioxidant activity in these mice. However, overexpression of Prdx6 had no protective effect on LDL oxidation in vitro, and transgenic mice fed an atherogenic diet for 10 weeks did not possess an increased resistance to atherosclerosis nor did they maintain the high prediet plasma HDL levels consistent with the Ath1-resistant phenotype. In addition, the Prdx6 allele from the susceptible strain was shown to have a higher antioxidant activity than that of the resistant strains. These data suggest that the increased peroxidase activity attributable to Prdx6 overexpression in transgenic mice is not sufficient to protect mice from atherosclerosis, and that Prdx6 is not likely to be the gene underlying Ath1.     

ATP binding cassette transporter A1 - key roles in cellular lipid transport and atherosclerosis

ATP-binding cassette transporter A1 (ABCA1) was recently recognized as the mutant molecule responsible for Tangier disease with low HDL levels, accumulation of cholesteryl esters in tissues, and increased risk of cardiovascular disease. Extensive studies for the past 2 years have recognized the critical role of ABCA1 in cholesterol and phospholipid trafficking. Since the removal of cholesterol from tissues is a key step in the prevention of atherosclerosis, significant attention has been focused on this molecule. Natural ABCA1 mutations in Tangier disease (TD) patients and WHAM chickens together with induced mutation in ABCA1 knock-out mice unequivocally established the important role of ABCA1 in maintaining circulating HDL levels and promoting cholesterol efflux from the arterial wall. Mice lacking ABCA1 showed similar phenotypes observed in Tangier disease patients with low levels of HDL. Further understanding of the roles of ABCA1 in lipid transport and atherosclerosis became clear from studies with ABCA1 transgenic mice. These mice showed enhanced cholesterol efflux from macrophages and reduced atherosclerotic lesion formation. The promoter of the ABCA1 gene has been mapped to a large extent, with the exception of cAMP response element. The present review summarizes recent developments on the role of ABCA1 in cholesterol efflux and prevention of atherosclerosis. Given the antiatherogenic properties of ABCA1, this molecule can serve as an appropriate target for developing drugs to treat individuals with low levels of HDL.     

Stress history increases alcohol intake in relapse: relation to phosphodiesterase 10A

Stressful experiences can result in elevated alcohol drinking, as exemplified in many individuals with post-traumatic stress disorder. However, how stress history, rather than acute stressors, influences alcohol intake remains uncertain. To model the protracted effects of past stress, male Wistar rats were subjected to light-cued footshock (stress history) or light cues alone (control) prior to acquisition of alcohol self-administration (1-hour sessions, fixed ratio 1-3, 100 μl of 10% v/v alcohol as reinforcer). Stress history did not alter mean alcohol intake during acquisition of self-administration, but it increased preference for the alcohol-paired lever over the inactive lever. Following an extinction period, rats with a history of stress exposure and low baseline alcohol intake showed a twofold elevation in alcohol self-administration, as compared with low-drinking rats with no stress history. Similar effects were not seen in rats self-administering 0.1% sucrose. Analysis of mRNA levels of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate and cyclic guanosine monophosphate hydrolyzing enzyme, showed that stress history increased Pde10a mRNA levels in the basolateral amygdala and, in low-drinking rats, the prelimbic prefrontal cortex (plPFC). Pde10a mRNA levels in the plPFC correlated directly with greater alcohol self-administration during the relapse-like phase, and greater BLA Pde10a mRNA levels correlated with increased ethanol preference after acquisition. The data demonstrate that stress history sensitizes otherwise low alcohol drinkers to consume more alcohol in a relapse-like situation and identify stress-induced neuroadaptations in amygdala and prefrontal cortical Pde10a expression as changes that may drive heightened alcohol intake and preference in susceptible individuals.     

LncRNA UCA1 sponges miR-206 to exacerbate oxidative stress and apoptosis induced by ox-LDL in human macrophages

Long noncoding RNA UCA1 has exerted a significant effect in cardiovascular disease. The biological role of UCA1 in atherosclerosis is unclear. Our study was to identify the potential mechanisms in the progression of atherosclerosis. Here, we observed that ox-LDL increased UCA1 expression greatly in THP-1 cells. Knockdown of UCA1 greatly inhibited CD36 expression, a crucial biomarker in atherosclerosis. Meanwhile, 20 μg/ml ox-LDL induced foam cell formation, which can be reversed by downregulation of UCA1. In addition, TC and TG levels induced by ox-LDL was rescued by UCA1 small interfering RNA. Accumulating studies have indicated that oxidative stress contributes to atherosclerosis progression. Here, we also found that reactive oxygen species, MDA, and THP-1 cell apoptosis were restrained by decreased of UCA1 with an increase of the superoxide dismutase activity. Moreover, miR-206 was predicted as a target of UCA1 and knockdown of UCA1 was able to repress miR-206 expression. Furthermore, overexpression of miR-206 inhibited oxidative stress process and it was reversed by UCA1 upregulation in vitro. In conclusion, we indicated that UCA1 sponged miR-206 to exacerbate atherosclerosis events induced by ox-LDL in THP-1 cells.     

Is it just paraoxonase 1 or are other members of the paraoxonase gene family implicated in atherosclerosis?

PURPOSE OF REVIEW: During the past decade, paraoxonase 1, a HDL-associated protein, has been demonstrated to be an important contributor to the antioxidant capacity of HDL. Studies using paraoxonase 1 null mice by gene targeting and transgenic mice corroborated the hypothesis that paraoxonase 1 protects against atherosclerosis. In contrast to paraoxonase 1, the other two members of the paraoxonase gene family, namely paraoxonase 2 and paraoxonase 3, are either undetectable (paraoxonase 2) or detected at very low levels (paraoxonase 3) on HDL, and are considered to participate in intracellular antioxidant mechanisms. In this review, we summarize studies reported in the past 2 years suggesting a protective role for paraoxonase 2 and paraoxonase 3 in the development of atherosclerosis in mice. RECENT FINDINGS: Adenovirus-mediated expression of human paraoxonase 2 or paraoxonase 3 proteins protects against the development of atherosclerosis in apolipoprotein E-deficient mice. Paraoxonase 2-deficient mice develop significantly larger atherosclerotic lesions than their wild-type and heterozygous counterparts on an atherogenic diet despite having lower levels of apolipoprotein B-containing lipoproteins. Atherosclerotic lesions were significantly lower in male hPON3Tg/LDLR null mice than in LDLR null mice on a western diet. SUMMARY: We conclude that, in addition to paraoxonase 1, both paraoxonase 2 and paraoxonase 3 proteins are protective against the development of atherosclerosis in mice. These findings underscore the utility of all members of the paraoxonase gene family as therapeutic targets for the treatment of atherosclerosis.     

HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis

High-density lipoprotein (HDL) has been identified as a potential target in the treatment of atherosclerotic vascular disease. The failure of torcetrapib, an inhibitor of cholesteryl ester transfer protein (CETP) that markedly increased HDL levels in a clinical trial, has called into doubt the efficacy of HDL elevation. Recent analysis suggests that failure may have been caused by off-target toxicity and that HDL is functional and promotes regression of atherosclerosis. New studies highlight the central importance of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 in reducing macrophage foam cell formation, inflammation, and atherosclerosis. A variety of approaches to increasing HDL may eventually be successful in treating atherosclerosis.     

Poor Lung Function Has Inverse Relationship with Microalbuminuria,an Early Surrogate Marker of Kidney Damage and Atherosclerosis: The 5th Korea National Health and Nutrition Examination Survey

Background

Despite epidemiological evidences of relationship between poor lung function and atherosclerosis, the relationship between poor lung function and microalbuminuria (MAU), an early surrogate marker of both kidney damage and atherosclerosis, is not well understood. Hence, we plan to investigate the relationship between poor lung function and MAU using multivariate models to adjust for other atherogenic risk factors.

Methods

We used data from the 5^th Korean National Health and Nutrition Examination Survey. Poor lung function is determined by spirometric measurement, primarily through estimation of the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Declines in the percent predicted FVC (<80%) and in the FEV₁/FVC ratio (<0.7) are defined as restrictive and obstructive patterns, respectively. Urine albumin to urine creatinine levels ratio (UACR) were measured in spot urine samples. MAU was defined as UACR >30 mg/g.

Results

Inverse relationship was observed between lung function and UACR. In an age-adjusted regression model, the regression coefficient (B) of 10% lower FVC was 11.09 in men (P = 0.002), which remained significant after adjustment for SBP, FBG, triglyceride level, BMI, smoking history, and heavy alcohol consumption (B = 7.52, P = 0.043). When the restrictive pattern was compared to the normal pattern, the odds ratios (OR) (95% confidence interval, 95%CI) for MAU were 1.90 (1.32–2.72) in men, after adjustment for age, hypertension, diabetes mellitus, triglyceride level, obesity, smoking history, physical activity, and heavy alcohol consumption.

Conclusions

Our study, the first investigation in Asia, demonstrated that the restrictive pattern is related to MAU in men. Furthermore, there was linear relationship between lower FVC and UACR. Thus, our current study suggests that poor lung function, particularly the restrictive pattern, is related to kidney damage as well as atherosclerosis.     

The role of maternal alcohol damage on ethanol teratogenicity in the rat

To study the severity and degree of in utero alcohol effects in relation to the rate of maternal alcohol damage, multiparous 1-year alcohol-fed rats were used, with an appropriate pair-fed control group. During pregnancy, alcoholic dams showed relatively high acetaldehyde levels (41 +/- 19 mumol/l) and blood alcohol levels of 22.8 +/- 14 mmol/l. They also showed marked histological alterations in liver as well as high serum aspartate-aminotransferase, alanine-aminotransferase, alkaline phosphatase, glutamate dehydrogenase, and gamma-glutamyltransferase activities. The increase in serum enzyme levels did not correlate with an increase in hepatic enzyme levels since only glutamate dehydrogenase was enhanced in liver after 1 year of alcohol intake. In addition, except for an increase in low Km aldehyde dehydrogenase activity, there were no changes in liver alcohol metabolizing enzymes in chronic alcohol vs. pair-fed females. Alcoholic rats showed a high incidence of damage in their progeny (resorptions, immature fetuses, decrease in fetal weight, etc.), and rats with the highest serum levels of the above enzymes (especially glutamate dehydrogenase and gamma-glutamyl transferase) had severely affected progeny. Rats with minimal histological liver damage, in contrast, did not show resorptions. Thus, the results presented suggest that the stage of maternal alcohol illness, as indicated mainly by the extent of liver damage, plays an important role in the frequency and severity of in utero alcohol effects in the rat.     

Soluble FcgammaRIIIa(Mphi) levels in plasma correlate with carotid maximum intima-media thickness (IMT) in subjects undergoing an annual medical checkup

Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express FcgammaRIIIa (CD16) identical to that in NK cells, but with a cell type-specific glycosylation, and these soluble forms (sFcgammaRIIIa) are present in plasma. We measured sFcgammaRIIIa(Mphi) derived from macrophages in plasma from subjects undergoing an annual medical checkup. The levels of sFcgammaRIIIa(Mphi) increased with age, and correlated positively with body mass index, blood pressure, LDL cholesterol to HDL cholesterol ratio, triglycerides, hemoglobin A1c, and creatinine, but negatively with HDL-cholesterol levels. The sFcgammaRIIIa(Mphi) levels were related to the number of risk factors for atherosclerosis: such as aging, current smoking, diabetes, hypertension, hyper-LDL-cholesterolemia, hypo-HDL-cholesterolemia, and family history of atherosclerotic diseases. In addition, the sFcgammaRIIIa(Mphi) levels were correlated with carotid maximum intima-media thickness (IMT). These findings indicate the macrophages are activated during the incipient stage of atherosclerosis, and suggest sFcgammaRIIIa(Mphi) may be used as a predictive marker for atherosclerosis.     

Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways

Atherosclerosis, the leading cause of death in developed countries, has been linked to hypercholesterolemia for decades. More recently, atherosclerotic lesion progression has been shown to depend on persistent, chronic inflammation in the artery wall. Although several studies have implicated infectious agents in this process, the role of infection in atherosclerosis remains controversial. Because the involvement of monocytes and macrophages in the pathogenesis of atherosclerosis is well established, we investigated the possibility that macrophage innate immunity signaling pathways normally activated by pathogens might also be activated in response to hyperlipidemia. We examined atherosclerotic lesion development in uninfected, hyperlipidemic mice lacking expression of either lipopolysaccharide (LPS) receptor CD14 or myeloid differentiation protein-88 (MyD88), which transduces cell signaling events downstream of the Toll-like receptors (TLRs), as well as receptors for interleukin-1 (IL-1) and IL-18. Whereas the MyD88-deficient mice evinced a marked reduction in early atherosclerosis, mice deficient in CD14 had no decrease in early lesion development. Inactivation of the MyD88 pathway led to a reduction in atherosclerosis through a decrease in macrophage recruitment to the artery wall that was associated with reduced chemokine levels. These findings link elevated serum lipid levels to a proinflammatory signaling cascade that is also engaged by microbial pathogens.     

ABCA1 gene expression in peripheral blood lymphocytes and macrophages in patients with atherosclerosis

ABCA1 transporter is known to play important role in the cholesterol transport from peripheral tissues. However its contribution in atherosclerosis development remains not completely understood. Using Real Time PCR, a significant reduction of ABCA1 mRNA level in leukocytes of patients with atherosclerosis was determined when compared with controls. Mean ABCA1 expression levels in leukocytes for the group of patients and for the control group are 0.57 +/- 0.28 and 0.93 +/- 0.14 (p = 0.02). At the same time we detected a significant increase of ABCA1 mRNA level in macrophages of patients when compared with controls. Mean ABCA1 expression levels in macrophages for the group of patients and for the control group are 1.32 +/- 0.10 and 0.90 +/- 0.14 (p = 0.014). In summary, we suggest that expression level of ABCA1 gene may contribute to the development of atherosclerosis.