Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies in humans have demonstrated the hypocholesterolemic effect of plant sterol consumption. It is unclear whether plant sterols regulate lipoprotein metabolism in the liver and intestines, thereby decreasing the levels of circulating atherogenic lipoproteins. We investigated the effect of the three main phytosterols: stigmasterol, campesterol, and beta-sitosterol on lipoprotein production in HepG2 human liver cells and Caco2 human intestinal cells and the mechanisms involved. Cells were incubated for 24h with 50 micromol/L of the different phytosterols or 10 micromol/L of atorvastatin. Very low-density lipoprotein levels (measured by apolipoprotein (apo) B100) in HepG2 cells and chylomicron levels (measured by apoB48) in Caco2 cells were measured using western blotting. Intracellular cholesterol levels were measured using gas chromatography. Analysis was carried out using Student's t-test and ANOVA. Secretion levels of apoB100 significantly decreased by approximately 30% after incubation with all phytosterols compared to control. In addition, cholesterol ester (CE) concentrations significantly decreased when HepG2 cells were incubated with the phytosterols compared to control cells. Secretion of apoB48 from intestinal cells significantly decreased by 15% with stigmasterol, 16% with campesterol and 19% beta-sitosterol compared to control. Collectively the data suggests that plant sterols limit lipid (CE) availability in cells. Decreases in circulating levels of LDL and chylomicron remnants seen in humans with the consumption of margarine phytosterols are possibly due to their effect on lipid production in cells and would therefore reduce the risk of developing cardiovascular disease.
Atherosclerosis 2005 Sep
PMID:Margarine phytosterols decrease the secretion of atherogenic lipoproteins from HepG2 liver and Caco2 intestinal cells. 1611 72

Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) are two herbs used in traditional Chinese medicine, most commonly for their putative cardioprotective and anti-atherosclerotic effects. In this study, we investigated the effect of a preparation of these herbs on two key processes in the early stages of atherosclerosis; macrophage lipid loading and monocyte adhesion to endothelial cells. Human monocyte derived macrophages (HMDMs) were treated with 0.1-1.0 mg/ml of the herbal mixture in aqueous buffers and loaded with acetylated LDL (AcLDL) (50 microg/ml) for 72 h, and analyzed for cholesterol (C) and cholesteryl esters (CE), via HPLC. Human endothelial cell monolayers were also treated with 0.1-1.0 mg/ml of the herbal mixture and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were assessed via ELISA. Compared to control conditions, the herbal mixture induced a significant dose-related decrease in the total cholesterol (free and esterified) in the HMDMs (p<0.001 by ANOVA). By contrast, the herbs also induced an increase in ICAM-1 expression (p<0.001) and monocyte adhesion at higher concentrations (p<0.05). In conclusion, treatment of cells with this preparation of Danshen and Gegen, a commonly used Chinese health supplement, results in a dose-related suppression of AcLDL uptake by human macrophages, and an increase in the level of ICAM-1 expression and adhesion of monocytes to endothelial cells. These herbs therefore show the ability to modulate key early events in atherosclerosis.
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PMID:Chinese herbs Danshen and Gegen modulate key early atherogenic events in vitro. 1633 13

It has been demonstrated that higher degree of arteriolar retinopathy is associated with greater cardiovascular risk, and hyperhomocysteinaemia is also related to increased cardiovascular risk, but interacts with other risk factors, particularly smoking. It still remains unclear regarding relationships of smoking, fasting plasma total homocysteine (tHcy) levels and arteriolar retinopathy. This study was aimed to investigate the relationship and influence of smoking and tHcy levels on degree of arteriolar retinopathy. Two hundred and forty-three subjects were enrolled from an annual health examination. The arteriolar retinopathy was examined by direct ophthalmoscopy. Dundett ANOVA showed that geometric mean of tHcy levels were 11.5+/-1.54 versus 11.2+/-1.41 versus 17.6+/-1.92 (P1=0.883, P2=0.001) in subjects with no arteriolar retinopathy (as control group), grades I and II retinopathy, respectively. Furthermore, multiple linear regression analysis showed that only smoking consumption (P<0.001), gender (P=0.012) and presence of hypertension (P=0.041) were independent determinants of plasma tHcy levels. After females were excluded, T-test showed a significant differences in tHcy levels (15.6+/-1.56 micromol/L versus 12.4+/-1.45 micromol/L, P=0.003) and in prevalence of grade II retinopathy (25.4% versus 9.3%, P=0.029), but no difference in other variables or prevalence of overall retinopathy between smokers and non-smokers. Finally, logistic regression showed that smoking (OR 4.19, 95% CI 1.17-15.0) was a stronger predictor than hyperhomocysteinaemia (OR 2.14, 95% CI 0.85-5.41) for presence of grade II retinopathy. This study showed that smoking was related to increased plasma tHcy levels in subjects with grade II retinopathy, and it could independently contribute to facilitating the progression of arteriolar retinopathy.
Atherosclerosis 2005 Nov
PMID:Smoking, homocysteine and degree of arteriolar retinopathy. 1621 92

Atherosclerosis, and its most common manifestation, coronary artery disease (CAD), are rather common causes of morbidity and mortality worldwide. Recognition of its various risk factors is important to planning effective preventive measures. After the homocysteine theory was presented in 1969, attention has been directed toward the serum homocysteine level as a coronary artery disease risk factor. The authors aimed to assess the relationship between hyperhomocysteinemia and CAD in an Iranian population. In a case control study, 197 individuals (male: 123 [62.4%]) who were scheduled for coronary angiography were selected. Venous samples were taken from the patients in fasting state before angiography. Data about age, sex, risk factors (eg, hypertension, diabetes, smoking, hyperlipidemia, obesity) were obtained from prepared questionnaires. Homocysteine levels in patients were measured by ELISA method. A homocysteine level above 15 mumol/liter was considered high. Angiography reports and homocysteine levels were analyzed by independent sample t test, one-way ANOVA, multiple linear regression, and stratified analysis. In comparison with the patients with normal angiography reports (32.5%), patients with abnormal angiography reports (67.5%) had increased levels of homocysteine (p = 0.001). About 28.1% of patients with normal angiography reports had hyperhomocysteinemia. After further evaluation, linear correlations were detected between the numbers of involved vessels and homocysteine level (p = 0.000). Multiple linear regression analysis of data detected that in individuals without any risk factors, the relationship was stronger and more meaningful (p = 0.000). These data show that hyperhomocysteinemia is related to CAD as an independent risk factor. In individuals without any risk factors a linear correlation between homocysteine level and numbers of coronary artery involvement was present. If this equation is confirmed prospectively in other studies, the level of plasma homocysteine may he used as a noninvasive way of predicting the number of diseased coronary arteries.
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PMID:Homocysteine level and coronary artery disease. 1644 51

The proinflammatory mediator CD40 ligand plays an important role in atherogenesis. Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared the effects of these therapies either alone or in combination on plasma soluble CD40 ligand (sCD40L). This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20mg and placebo, simvastatin 20mg and losartan 100mg, or losartan 100mg and placebo daily during each 2 month treatment period. Simvastatin alone did not significantly reduce sCD40L levels relative to baseline measurements when the entire cohort was analyzed. However, simvastatin significantly reduced sCD40L levels from 5.10+/-0.34 to 3.07+/-0.43ng/ml (P=0.002) in a subgroup of 18 patients with high baseline sCD40L levels >2.95ng/ml. Combined therapy or losartan alone significantly decreased plasma sCD40L levels relative to baseline measurements by 14+/-7% (P=0.001) and 13+/-10% (P=0.001), respectively. These decreases were significantly greater than those observed with simvastatin alone (P=0.023 by ANOVA). Significant inverse correlations between baseline sCD40L levels and percent changes in sCD40L levels were observed (r=-0.456, P=0.001 after simvastatin alone; r=-0.476, P<0.001 after combined therapy; r=-0.451, P=0.002 after losartan alone). Losartan alone or combined therapy significantly reduced plasma sCD40L levels more than simvastatin alone in our subjects. Simvastatin, losartan and combined therapy significantly reduced sCD40L to the greatest extent in patients with high baseline sCD40L levels.
Atherosclerosis 2007 Jan
PMID:The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients. 1650 Jun 62

There is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and cerebrovascular disease. The aim of the study was to elucidate the relationship between the polysomnographically (PSG) measured severity of OSA and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. 147 patients (102 males, 45 females) referred to our sleep laboratory for evaluation of snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein (hs-CRP) and fibrinogen and four sonographic indices: intima-media thickness (IMT) of the common carotid artery (CCA), IMT from bulb to internal carotid artery (Bulb-ICA), combined IMT measurements from all segments and a plaque score (PlaS). Pearson correlation analysis, intergroup comparison (ANOVA), covariance analysis and a multiple regression were performed to assess the association between surrogate markers and respiratory variables. 44 patients had no OSA (apnea-hypopnea index AHI < 5/h), 27 mild (AHI 5-15), 25 moderate (AHI 15-30) and 51 severe OSA (AHI > 30). After adjusting for potential confounders, significant differences between the controls and all three OSA groups were observed in the CCA-IMT (p = 0.032) and in the PlaS between the controls and the severe group (p = 0.034). Multiple regression revealed the AHI as an independent predictor of CCA-IMT (p = 0.001) and combined IMT (p = 0.001), whereas the percentage of total sleep time with an oxygen saturation below 90 % was associated with Bulb-ICA IMT (p = 0.018) and hs-CRP (p = 0.015). OSA is associated with higher surrogate levels of cerebrovascular disease. Even mild OSA seems to predispose to early atherosclerosis.
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PMID:Structural and serum surrogate markers of cerebrovascular disease in obstructive sleep apnea (OSA): association of mild OSA with early atherosclerosis. 1651 51

It is known that antioxidants have an important role in the prevention of coronary artery disease (CAD). Low total antioxidant capacity (TAC) is a risk factor for ischemic heart disease. However, no data are available concerning the relationship between TAC and severity of thoracic aortic atherosclerosis. This study using multiplane transesophageal echocardiography (TEE) examined the relationship between atherosclerotic thoracic aortic intima-media thickness (TAIMT) and TAC. Twenty-nine patients (17 male, 12 female; mean age 36 +/- 8 years) without a history of atherosclerotic cardiovascular disease referred for TEE were included. The patients with obesity, hypertension, diabetes, and CAD were excluded. The TAC was measured for each patient using a more recently developed method. TAIMT and grade of thoracic aortic atherosclerosis were evaluated in each patient by using TEE. Mean TAC level was 1.91 +/- 0.53 mmol Trolox equiv/l. There was a negative and significant correlation between the TAC levels and TAIMT and grade of thoracic aortic atherosclerosis (r = -0.799, P < 0.001 versus r = -0.827, P < 0.001, respectively). Multiple linear regression analysis showed that TAIMT was independently associated with TAC (beta = -0.734, P < 0.001). The mean values of TAC in grade I, II, and III were 2.23 +/- 0.31, 1.58 +/- 0.31, and 1.04 +/- 0.27 mmol Trolox equiv/l, respectively (ANOVA P < 0.001). This study indicates that the TAC is an independent variable for TAIMT and it has a potential for an independent variable for atherosclerotic lesions in the major arterial locations.
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PMID:Relationship between plasma total antioxidant capacity and thoracic aortic intima-media thickness. 1652 87

CETP (cholesteryl ester transfer protein) and HL (hepatic lipase) play a role in the metabolism of plasma lipoproteins, but the effects of CETP and LIPC (gene encoding HL) genotypes on coronary atherosclerosis may be dependent on LDL (low-density lipoprotein)-receptor activity. Recently, the -1337 C>T polymorphism in the CETP gene has been reported in REGRESS (Regression Growth Evaluation Statin Study) to be a major determinant of promoter activity and plasma CETP concentration. In the present study, we have investigated the effects of the CETP promoter -1337 C>T and LIPC promoter -514 C>T polymorphisms on serum lipid profiles and risk of coronary atherosclerosis in 206 patients (154 males) with heterozygous FH (familial hypercholesterolaemia). To evaluate coronary atherosclerosis, we used CSI (coronary stenosis index) calculated from coronary angiograms. The CETP -1337 T allele was less frequent in subjects with a CSI > or =14 (mean value) in the group with coronary artery disease (P=0.04, as determined by chi(2) test). ANOVA revealed that HDL-C (high-density lipoprotein-cholesterol) and triacylglycerol (triglyceride) levels were not significantly higher in the presence of the CETP promoter -1337 T allele. Combined with LIPC promoter polymorphisms, HDL-C levels were highest and CSI were lowest with CETP -1337 CT+TT and LIPC -514 CC genotypes, but a significant interaction was not shown. A multiple logistic regression analysis revealed that, in patients with coronary atherosclerosis, the CETP- 1337 CC genotype was a significant genetic risk factor in FH (odds ratio=2.022; P=0.0256). These results indicate that the CETP promoter -1337C>T polymorphism is associated with the progression of coronary atherosclerosis in Japanese patients with FH, independent of HDL-C and triacylglycerol levels.
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PMID:CETP (cholesteryl ester transfer protein) promoter -1337 C>T polymorphism protects against coronary atherosclerosis in Japanese patients with heterozygous familial hypercholesterolaemia. 1682 36

Tissue factor (TF) plays a pivotal role in thrombus formation. Statins and angiotensin converting enzyme inhibitors attenuate expression of TF by distinct mechanism. Therefore, we hypothesized that combined therapy with simvastatin and ramipril may have additive beneficial anti-atherogenic effects to lower TF activity when compared with either drug alone. This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each treatment period. Simvastatin and ramipril monotherapy tended to reduce TF activity (0.53 to 0.46 nM, P=0.056; 0.54 to 0.50 nM, P=0.167, respectively) while combined therapy had a significant effect (0.64 to 0.43 nM, P<0.001). All three therapies significantly reduced prothrombin fragment 1+2 (F1+2) levels from their respective baselines (P=0.037, P<0.001, and P=0.057, respectively). Combined therapy significantly reduced TF activity and F1+2 levels to a greater extent than either simvastatin or ramipril alone (P=0.029 and P=0.040 by ANOVA, respectively). Percent changes in TF activity and percent changes in F1+2 levels were significantly correlated. All three therapies reduced CD40 ligand levels from their respective baselines (P=0.098, P<0.001, and P=0.002, respectively) with no significant differences among these three therapies (P=0.204 by ANOVA). Ramipril combined with simvastatin significantly reduces plasma TF activity and F1+2 levels to a greater extent than monotherapy with either drug in patients with type 2 diabetes.
Atherosclerosis 2007 Sep
PMID:Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes. 1696 76

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-alpha by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 microg/mL and 200 microg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 microg/mL) increased the production of TNF-alpha 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.
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PMID:Triggering of inflammatory response by myeloperoxidase-oxidized LDL. 1716 45


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