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)

Abnormal endothelium-dependent vasodilatation is well documented in coronary artery disease (CAD), as are significant increases of acute phase inflammatory proteins and other soluble hepatic and endothelium derived proteins. In the current study we investigated whether there is a relationship between endothelium-dependent vasodilatation and the plasma levels of such proteins. Further we examined the association between these proteins, together with age, cholesterol and endothelium function, and participant status (i.e. healthy, smoker, coronary artery disease). Three groups of participants were recruited: healthy controls (n = 20), cigarette smokers (n = 20) and patients with coronary artery disease (n = 20). Forearm vascular dilatation responses to the endothelium-dependent agonist acetylcholine were obtained using venous occlusion plethysmography. Blood was sampled at the time of study for the measurement of the serological proteins described above. Responses to acetylcholine were significantly dampened in patients with CAD when compared with control and smoker groups (forearm blood flow at acetylcholine 37 microg/min): control, smokers, CAD, 12.14 +/- 2.14, 12.35 +/- 09.4, 5.12 +/- 0.81, ANOVA, P < 0.05). Responses to acetylcholine were not different between controls and smokers. C-reactive protein (C-RP) levels (controls, smokers, CAD, 1.40 +/- 0.19, 2.27 +/- 0.71, 4.73 +/- 1.09, P < 0.05) and protein S levels were significantly higher in the CAD group compared with the other two groups. There was a significant inverse correlation between forearm blood flow responses to acetylcholine and C-reactive proteins. Both responses to acetylcholine and C-RP levels demonstrated a significant association with participant status with the r value increasing from 0.405 for responses to acetylcholine to 0.491 for the combination of responses to acetylcholine and C-RP. We conclude that there is an inverse correlation between C-reactive protein, but not protein S, VCAM-1, P-selectin nor von Willebrand factor, levels and abnormal endothelium-dependent vasodilation and further that responses to acetylcholine together with C-RP protein have a strong association with cardiovascular risk and disease.
Atherosclerosis 2004 Feb
PMID:Plasma C-reactive protein, but not protein S, VCAM-1, von Willebrand factor or P-selectin, is associated with endothelium dysfunction in coronary artery disease. 1538 Apr 69

Diet-induced changes in serum lipoproteins are a major risk factor for the development of atherosclerosis, the leading cause of mortality in Westernized countries. Atherosclerosis is now appreciated to be a systemic inflammatory disease where increased synthesis of inducible proteins by the liver, such as C-reactive protein (CRP) and others, may play roles in accelerating the disease process. To systematically investigate the genetic response of the liver to diet-induced atherosclerosis, we applied high-density microarray technology in a mouse model of atherosclerosis (LDLR-/- mouse). LDLR-/- mice and congenic (LDLR+/+) controls were placed on low-fat (LF) or high-fat (HF) Western-style diets. The Western diet produced sustained elevations in total cholesterol (2.5-fold for LDLR+/+, 5.0-fold LDLR-/-) relative to the respective LF groups. Tissues were harvested after 12 wk when significant atherosclerotic lesion development was first detectable by en face histomorphometry of oil red O-stained aortas. Diet, rather than genotype, was most highly associated with development of atherosclerotic lesions. Liver mRNA expression profiles of triplicate animals from each group were determined by high-density oligonucleotide microarrays; and genes with transcript levels influenced by genotype and diet were identified by two-way ANOVA. Approximately one-third of the 102 genes identified to be altered by diet [Pr(F) < 0.0005] were involved in lipid metabolism. In addition, we identified components of the alternative complement pathway, including C3, properdin, and factor D, for which mRNA levels were independently confirmed by quantitative real-time RT-PCR analysis, and C3 protein was demonstrated in aortic lesions by immunostaining. These findings suggest that induction of the alternative complement pathway may be an additional mechanism by which a high-fat/Western diet accelerates atherosclerosis.
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PMID:Liver gene expression associated with diet and lesion development in atherosclerosis-prone mice: induction of components of alternative complement pathway. 1523 19

Angiotensin II stimulates the expression of tissue factor (TF) and plasminogen activator inhibitor type-1 (PAI-1), and AT1 receptor blockade (ARB) reduces PAI-1 and TF activities in experimental studies. We investigated the effects of ARBs on TF activity, tissue plasminogen activator (tPA), PAI-1 antigen levels, plasma renin activity (PRA) and aldosterone levels in hypertensive patients. Placebo, losartan 100mg, irbesartan 300 mg, and candesartan 16 mg daily were administered to 122 patients for 2 months. Compared with placebo, ARBs significantly reduced TF activity (P <0.001 by ANOVA), and candesartan was the most potent. Compared with placebo or losartan, irbesartan and candesartan significantly lowered plasma levels of PAI-1 antigen (P <0.001 by ANOVA) with no differences between the two. Compared with placebo, all ARBs lowered plasma levels of aldosterone (P=0.012 by ANOVA) and increased PRA (P=0.005 by ANOVA). There were significant correlations between the degree of change in TF activity and PAI-1 antigen levels (r=0.458, P <0.0001) and between the change in TF activity and PRA (r=-0.296, P=0.006), but not with the magnitude of reduction in blood pressure following ARB therapy. ARBs significantly reduced TF activity, PAI-1 antigen levels, and aldosterone levels in hypertensive patients. The clinical significance of the varying potency of some ARBs needs to be further investigated.
Atherosclerosis 2004 Nov
PMID:Angiotensin II type 1 receptor blockers reduce tissue factor activity and plasminogen activator inhibitor type-1 antigen in hypertensive patients: a randomized, double-blind, placebo-controlled study. 1548 78

There is strong and consistent evidence across numerous studies that social isolation or lack of social support is an independent risk factor for incident coronary heart disease. However, the impact of social isolation or lack of social support on the progression of coronary atherosclerosis in women has not been well documented. Among 292 women, aged 30-65 years, consecutively hospitalized with acute myocardial infarction or unstable angina between 1991 and 1994 enrolled in the female coronary risk study, 102 women were available to study disease progression over an average of 3.2 years. Three aspects of social support were studied: emotional support, social integration, and interpersonal social relations. Quantitative coronary angiography was performed 3-6 months following index hospitalization and repeated 3 years later. Progression of coronary atherosclerosis was evaluated as the change in mean luminal diameter from first to second measurements of 10 pre-defined coronary segments. Mixed model ANOVA was used to analyze the impact of social support on progression of coronary atherosclerosis. Significantly greater coronary atherosclerosis progression was found among women who lacked emotional support (mean coronary artery luminal diameter narrowing by 0.15 mm), with social isolation (0.14 mm), and lack of interpersonal social relations (0.13 mm), whereas women with high levels of support progressed less. It was 0.05 mm in women with high levels of emotional support, 0.07 mm for socially integrated women, and 0.04 mm in women with adequate interpersonal social relations. These associations were independent of conventional clinical and lifestyle factors such as age, smoking history, body mass index, menopausal status, and diagnosis of index event of acute myocardial infarction. The results of our study suggest that lack of emotional support, social isolation, and lack of interpersonal social relations are important risk factors for accelerated progression of coronary atherosclerosis in middle-aged women.
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PMID:Influence of social support on progression of coronary artery disease in women. 1555 Mar 7

Current concepts for the explanation of endothelial dysfunction and accelerated atherosclerosis in uremia propose a reduced vascular bioavailability of nitric oxide (NO). The aim of the present study was to test the contributions of NO and NO/prostacyclin (PGI(2))-independent mechanisms to both baseline vascular tone and agonist-induced endothelium-dependent vasodilation in patients on hemodialysis (HD). In 10 HD patients and eight matched healthy control subjects, forearm blood flow (FBF) was measured at rest and during intrabrachial infusions of norepinephrine (NE; endothelium-independent vasoconstrictor, 60, 120, and 240 pmol/min) and N-monomethyl-L-arginine (blocker of NO synthases, 16 micromol/min). After inhibition of cyclo-oxygenase by ibuprofen (1200 mg orally), endothelium-dependent and -independent vasodilation was assessed by infusion of acetylcholine (ACh; 1, 5, 10, 50, 100, and 300 nmol/min) and sodium-nitroprusside (2.5, 5, and 10 microg/min). NO/PGI(2)-independent vasodilation was tested by equal infusions of ACh during NO clamp. N-monomethyl-L-arginine reduced resting FBF to a comparable degree in both groups. Vascular responses to ACh were reduced in HD (P = 0.003 versus control by ANOVA), whereas those to sodium nitroprusside were mainly at control level. Infusion of ACh during NO clamp caused a similar increment of FBF in both groups. NO-mediated vasodilation as calculated by the difference between ACh-induced responses without and with NO clamp was substantially impaired in HD (P < 0.001) compared with control. In HD patients, baseline NO-mediated arteriolar tone is at control level. This study provides first evidence that endothelial dysfunction of uremic patients as shown by reduced agonist-induced endothelium-dependent vasodilation is attributable to reduced stimulation of NO, whereas the NO/PGI(2)-resistant portion of ACh-mediated vasodilation is unaffected.
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PMID:Reduced agonist-induced endothelium-dependent vasodilation in uremia is attributable to an impairment of vascular nitric oxide. 1572 85

Acute mental stress may contribute to atherosclerosis by affecting inflammation and coagulation; however, the crosstalk between inflammation and coagulation during stress has not been studied. In the present study, we investigated the association of plasma fibrinogen, plasma IL-6 (interleukin-6) and free salivary cortisol with the procoagulant marker D-dimer reflecting fibrin formation both over a 2-h period and in response to acute mental stress. Twenty-one male volunteers (mean age, 47+/-8 years) underwent the Trier Social Stress Test combining a 3-min preparation phase, a 5-min job interview and 5-min mental arithmetic test before an audience. IL-6, fibrinogen, D-dimer and cortisol were measured immediately before and after stress, and after 45 min and 105 min of recovery from stress. Two distinct areas under the curve were computed to obtain integrated measures of total protein activity over the entire 2-h period and of stress reactivity of proteins. IL-6 (P < 0.001), fibrinogen (P = 0.001), D-dimer (P = 0.021) and cortisol (P < 0.001) had all significantly changed across the four time points assessed, as determined by ANOVA. For the entire 2-h period, total fibrinogen activity (R2 = 0.33, P = 0.007) and total cortisol activity (DeltaR2 = 0.17, P = 0.034) explained 50% of the variance in total D-dimer activity. Stress-induced changes in fibrinogen (R2 = 0.47, P = 0.001) and IL-6 (DeltaR2 = 0.18, P = 0.008) together explained 65% of the variance in D-dimer reactivity to stress. Total fibrin formation was independently predicted by fibrinogen and hypothalamo-pituitary-adrenal activity. Pro-inflammatory and procoagulant changes with stress were associated. Aside from fibrinogen reactivity, IL-6 reactivity was an independent predictor of stress-induced fibrin formation.
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PMID:Different contribution of interleukin-6 and cortisol activity to total plasma fibrin concentration and to acute mental stress-induced fibrin formation. 1575 67

Apolipoprotein A-I/C-III/A-IV (apoA-I/C-III/A-IV) SstI and apolipoprotein B (apoB) XbaI polymorphisms have been shown to affect serum low-density lipoprotein (LDL) cholesterol concentrations in a sample of Finnish children. We studied whether these polymorphism are associated with carotid artery intima-media thickness (IMT), a marker of pre-clinical atherosclerosis, measured in the same subjects during their adulthood. A random sub-sample of 214 individuals from the "Cardiovascular Risk in Young Finns" study, for whom genotypes, cardiovascular risk factor data and carotid artery IMT measured in 2001 were available, were studied. Mean carotid IMT values increased according to the apoA-I/C-III/A-IV SstI genotype groups in the order of S1S1 (0.58+/-0.08 mm), S1S2 (0.61+/-0.08 mm), and S2S2 (0.70+/-0.16 mm, p=0.02, ANOVA). In multiple linear regression analysis after adjusting for age, sex and body mass index the mean IMT thickness among the S2 allele carriers was higher (p=0.02) compared to non-carriers. In logistic regression analysis the frequency of S2 allele carriers was higher among the high IMT group compared to the low IMT group (OR=4.02, CI: 1.68-9.61, p=0.002). No significant association between apoB XbaI polymorphism and carotid IMT was found. However, serum total and LDL cholesterol and apoB concentrations were significantly different among apoB genotype groups (p<0.001 for all traits). The apoA-I/C-III/A-IV SstI polymorphism is associated with carotid IMT in young Finns.
Atherosclerosis 2005 May
PMID:Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms and their association with carotid artery intima-media thickness in the Finnish population. The Cardiovascular Risk in Young Finns Study. 1582 78

The aims of this study were to determine whether non-invasive measurement of endothelial function in conduit arteries reflects that of subcutaneous resistance arteries measured in vitro and to examine whether there is an endothelial dysfunction also in resistance arteries in patients with a previous myocardial infarction. The brachial artery diameter responses to a hyperemic flow stimulus and an in vitro method, pressure myography, to directly evaluate flow-mediated responses in arteries obtained from biopsies of subcutaneous fat were measured in 25 patients with a previous myocardial infarction and in 8 aged matched healthy subjects. Flow-mediated dilatation of the brachial artery was more pronounced in the healthy group compared with the group with coronary disease, 5.1 +/- 2.5% and 2.6 +/- 2.1%, respectively (p < 0.05). The flow-mediated dilatation in subcutaneous arteries from CHD patients was significantly reduced compared to control subjects (e.g. percent change from initial preconstriction at maximum flow rate of 204 microl/min: 42 +/- 7% CHD (n = 25) versus 84 +/- 24% control (n = 8), ANOVA, p = 0.03). There was a significant correlation between flow-mediated dilatation of the brachial artery and maximum flow-mediated dilatation at microvascular level, (p < 0.01). In conclusion this study demonstrates endothelial dysfunction in both conduit and resistance circulation in patients after myocardial infarction compared to an aged-matched healthy control group. Furthermore, a significant and independent relationship between endothelial function by means of flow-mediated dilatation in large conduit arteries and resistance arteries was observed.
Atherosclerosis 2006 Jan
PMID:Endothelial function in conduit and resistance arteries in men with coronary disease. 1597 80

Calcium channel blockers slow the progression of atherosclerosis. The purpose of the present experiments was to examine the action of lacidipine in a condition that accelerates the development of atherosclerosis in order to test the hypothesis that the protective action of lacidipine in atherosclerosis is unrelated to the reduction of blood pressure. Male ApoE-deficient mice (6 weeks old) were exposed either to normal chow (ND) or to a Western-type diet (WD, adjusted calorie diet containing 42% from fat) for 8 weeks. Western-type diet induced a reduction of nitric oxide (NO)-mediated endothelium-dependent relaxation to acetylcholine (Max relaxation % = 55.8 +/- 2 for ND and 46.6 +/- 2 for WD, n = 8, p < 0.05). Dose-relaxation curves to S-nitroso-N-acetylpenicillamine (SNAP) NO donor were also significantly rightward-shifted (n = 7, ANOVA, p < 0.01) in WD compared with ND arteries. Chronic treatment of WD mice with lacidipine (1 and 3 mg/kg/day) increased significantly the acetylcholine-evoked relaxation (to 76.6 +/- 3.5%, n = 6, ANOVA, p < 0.001) and prevented the loss of responsiveness to SNAP in mice exposed to WD. Plasma renin activity and endothelin-1 plasma levels as well as thiobarbituric acid-reactive substance levels in kidneys were significantly lower in WD mice treated with lacidipine than in untreated ones. In mice exposed to WD lacidipine reduced extension of atherosclerotic lesions, renal injury and increase in blood pressure. Experimental data indicate that inhibition of Western-type diet-evoked alterations is related to both antioxidant and vasoactive properties of lacidipine.
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PMID:Calcium channel blocker inhibits Western-type diet-evoked atherosclerosis development in ApoE-deficient mice. 1602 Jun 30

The monoclonal theory of atherosclerosis postulates that a subpopulation of vascular smooth muscle cells (VSMCs) is selectively expanded in response to pathologic stimuli and accumulates in vascular intima. The purpose of this research was to clone VSMC, determine growth rates of the clones and their ability to release the mitogenic cytokine tumor necrosis factor-alpha (TNF-alpha). With approval of the institutional animal care and use committee, VSMCs were isolated and cultured from the thoracic aortas of three rats. To confirm that the cells in primary culture were of smooth muscle origin, they were immunostained with anti-alpha-smooth muscle-actin antibodies. Single cell-derived individual colonies with uniform appearance were surrounded by cloning rings, released with trypsin, and expanded. Growth rates of the clones were assessed by the mitochondrial dependent reduction of methyltetrazolium (MTT) to formazan after 24-hour stimulation with 10 per cent serum. Additionally, cloned cells were stimulated with 0.1, 1, 10, and 20 microg/mL lipopolysaccharide (LPS) for 24 hours, and TNF-alpha was determined in the culture medium. Data were analyzed by ANOVA. Two clones were isolated that could be divided into categories based on distinctly different morphology: 1) spindle-shaped (SP) or 2) epithelioid-shaped (EP) VSMCs. The SP clone had a growth rate that was 25 per cent higher than the EP clone (P < 0.05). Also, the SP clone had significantly higher release of TNF-alpha in response to LPS. For instance, TNF-alpha released in response to 0.1 microg/mL of LPS in the SP clone was 157 +/- 45 pg/mL versus 21 +/- 8.5 pg/mL in the EP clone (P < 0.05). Primary cultures of rat VSMCs are heterogeneous and consist of at least two morphologically distinct cell types. These clones are different in growth rate and cytokine production. It is possible that selective expansion of one of these clones contributes to formation of stenotic vascular lesions.
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PMID:Two distinct phenotypes of rat vascular smooth muscle cells: growth rate and Production of tumor necrosis factor-alpha. 1608 16


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