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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses three stages in the life history of an atheroma: initiation, progression and complication. Recruitment of mononuclear leucocytes to the intima characterizes initiation of the atherosclerotic lesion. Specific adhesion molecules expressed on the surface of vascular endothelial cells mediate leucocyte adhesion: the selectins and members of the immunoglobulin superfamily such as vascular cell adhesion molecule-1 (VCAM-1). Once adherent, the leucocytes enter the artery wall directed by chemoattractant chemokines such as macrophage chemoattractant protein-1 (MCP-1). Modified lipoproteins contain oxidized phospholipids which can elicit expression of adhesion molecule and cytokines implicated in early atherogenesis. Progression of atheroma involves accumulation of smooth muscle cells which elaborate extracellular matrix macromolecules. These processes appear to result from an eventual net positive balance of growth stimulatory versus growth inhibitory stimuli, including proteins (cytokines and growth factors) and small molecules (e.g. prostanoids and nitric oxide). The clinically important complications of atheroma usually involve thrombosis. Arterial stenoses by themselves seldom cause acute unstable angina or acute myocardial infarction. Indeed, sizeable atheroma may remain silent for decades or produce only stable symptoms such as angina pectoris precipitated by increased demand. Recent research has furnished new insight into the molecular mechanisms that cause transition from the chronic to the acute phase of atherosclerosis. Thrombus formation usually occurs because of a physical disruption of atherosclerotic plaque. The majority of coronary thromboses result from a rupture of the plaque's protective fibrous cap, which permits contact between blood and the highly thrombogenic material located in the lesion's lipid core, e.g. tissue factor. Interstitial collagen accounts for most of the tensile strength of the plaque's fibrous cap. The amount of collagen in the lesion's fibrous cap depends upon its rate of biosynthesis stimulated by factors released from platelets (e.g. transforming growth factor beta or platelet-derived growth factor), but inhibited by gamma interferon, a product of activated T cells found in plaques. Degradation by specialized enzymes (matrix metalloproteinases) also influences the level of collagen in the plaque's fibrous cap. Such studies illustrate how the application of cellular and molecular approaches has fostered a deeper understanding of the pathogenesis of atherosclerosis. This increased knowledge of the basic mechanisms enables us to understand how current therapies for atherosclerosis may act. Moreover, the insights derived from recent scientific advances should aid the discovery of new therapeutic targets that would stimulate development of novel treatments. Such new treatments could further reduce the considerable burden of morbidity and mortality due to this modern scourge, and reduce reliance on costly technologies that address the symptoms rather than the cause of atherosclerosis.
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PMID:Changing concepts of atherogenesis. 1076 52

The aim of the study was to evaluate the effects of the presence, extent, and clinical stability of coronary artery disease on endothelial function parameters, C-reactive protein and homocysteine levels. Fifty-eight patients with angiographically documented coronary artery disease and 25 patients with normal coronary arteries were evaluated for risk factors, plasma homocysteine, C-reactive protein, and soluble adhesion molecule levels. Vascular cell adhesion molecule-1 and sE-selectin were significantly higher in the group with coronary artery disease than in healthy subjects (p = 0.005 and p = 0.031, respectively). Patients with unstable angina had significantly higher C-reactive protein (p < 0.001), troponin I (p < 0.01), and leukocyte counts (p < 0.05) than those with stable angina. sE-selectin levels were correlated with the extent of coronary atherosclerosis (r = 0.444, p < 0.05), and plasma homocysteine levels were associated with vascular cell adhesion molecule-1 (r = 0.479, p < 0.05) in unstable cases. These results suggest that vascular cell adhesion molecule-1 and sE-selectin are useful for determining the presence of coronary atherosclerosis, whereas C-reactive protein, troponin 1, and leukocyte count are predictors of clinical stability.
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PMID:Extent of coronary atherosclerosis and homocysteine affect endothelial markers. 1157 Jun 57

Atherosclerosis is an inflammatory disease of the vessel wall characterized by monocyte infiltration in response to pro-atherogenic factors such as oxidized lipids. Recently, the role of specific adhesion molecules in this process has been explored. The endothelium overlying atherosclerotic lesions expresses P-selectin and the shoulder regions express vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), which is also expressed on endothelium in regions not prone to plaque development. Serum levels of soluble P-selectin, ICAM-1 and VCAM-1 are elevated in patients with angina pectoris or peripheral atherosclerotic disease. Reconstituted in vitro systems using monocytes on cytokine-activated endothelial cells under shear flow suggested the involvement of P-selectin, L-selectin, VCAM-1, its ligand, VLA-4 integrin and CD18 integrins. Studies of monocyte adhesion in isolated perfused carotid arteries harvested from atherosclerotic (apoE-/-) mice show a predominant involvement of P-selectin and its ligand P-selectin glycoprotein-1 (PSGL-1) in rolling and of VLA-4 and VCAM-1 in firm adhesion. Consistent with these findings, apoE-/- mice that are also deficient for P-selectin show significantly reduced atherosclerotic lesion sizes and are almost completely protected from neointimal growth after vascular injury. Milder effects are also seen in the low-density lipoprotein (LDL) receptor deficient (LDLR-/-) mouse. In a high cholesterol/cholate model, a role of ICAM-1 and CD18 integrins was also shown, but this awaits confirmation in more physiologic models. Transient blockade of the VLA-4/VCAM-1 adhesion pathway by antibodies or peptides in apoE-/- or LDLR-/- mice reduced monocyte and lipid accumulation in lesions. These data suggest that P-selectin, PSGL-1, VLA-4 and VCAM-1 are the most important adhesion molecules involved in monocyte recruitment to atherosclerotic lesions.
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PMID:Adhesion molecules and atherogenesis. 1167 24

It is hypothesized that adhesion molecules could be an early predictor of coronary artery disease. Therefore we investigated the relationship between the concentrations of soluble forms of adhesion molecules and disturbances of glucose metabolism in 78 men referred for coronary angiography but with no previous history of diabetes. The group consisted of 78 men (mean age, 47.6 +/- 7.0 years; mean body mass index [BMI], 28.4 +/- 3.24 with the symptoms of angina pectoris and positive exercise test. All subjects were given a standard oral glucose tolerance test (OGTT) with glucose and insulin estimations. Fasting plasma concentrations of the soluble (s) forms of E-selectin, intercellular adhesion cell molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and HbA(1c) were also measured. According to the OGTT, 10.2% of the patients (n = 8) fulfilled the criteria for type 2 diabetes mellitus and 44.9% (n = 35) for impaired glucose tolerance (IGT). The highest concentrations of sE-selectin were observed in patients with type 2 diabetes mellitus and were significantly higher in comparison to the group with normal glucose tolerance and IGT. The concentration of sVCAM-1 increased with the progression of disturbances of glucose metabolism and remained the highest in type 2 diabetic patients. sICAM-1 concentration was not significantly different. sE-selectin concentration correlated significantly with fasting glucose (r = 0.23, P =.041), postload glucose (r = 0.39, P =.001), and postload insulin (r = 0.28, P =.023). sVCAM-1 was significantly related to the postload glucose concentration (r = 0.30, P =.009). A significant correlation between sICAM-1 concentration and postload insulin was also observed (r = 0.27, P =.025). This would suggest that hyperglycemia increases sE-selectin and sVCAM-1 in plasma, which reflects excessive formation of atherosclerotic plaques in patients with disturbances of glucose metabolism.
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PMID:Circulating E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in men with coronary artery disease assessed by angiography and disturbances of carbohydrate metabolism. 1203 26

The Epidemiological Study of Myocardial Infarction Study which enrolled 9758 apparently healthy men aged 50-59 years, is a prospective cohort study designed to evaluate markers of coronary risk. Soluble forms of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured in plasma obtained at baseline from 317 subjects who suffered a coronary event during the 5-year follow-up and in twice the number of control subjects who were matched for center, age and day of inclusion in a nested case-control design. The relative risk associated with the highest compared with the lowest thirds of ICAM-1 (>625 versus <502 ng/ml) was 2.45 (95% CI: 1.64-3.65, P<0.001) without adjustment; it decreased moderately (RR: 2.09; 95% CI: 1.34-3.24, P<0.001) after control for lipid and non-lipid factors and remained significantly elevated after adjustment for C-reactive protein (CRP) (RR: 1.90; 95% CI: 1.21-2.96, P=0.005). Plasma ICAM-1 was essentially associated with the risk of myocardial infarction or coronary death and also with angina pectoris. Subjects with CRP presented elevated coronary risk only if ICAM-1 was high. An elevated level of VCAM-1 was not associated with any risk of future acute coronary event, or with angina pectoris. This data indicates that plasma levels of ICAM-1 may serve as risk markers for future coronary events whatever their clinical presentation and that risk is better defined using simultaneous measurements of ICAM-1 and CRP than any of these levels separately.
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PMID:Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME Study. 1517 38

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective analysis of the data from several clinical trials reveals that clinical depression is associated with enhanced activation of platelet/endothelial biomarkers even above the level expected in ACS. These findings may contribute to the unfavorable outcome associated with clinical depression in patients with ACS.
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PMID:Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials. 1296 Jun 10

Studies have shown disparate results in relation to the role of plasma concentrations of inflammation markers such as fibrinogen, cytokines, and cell adhesion molecules in acute coronary syndromes. The differentiation of primary versus secondary alterations of these markers in response to acute coronary syndromes is not clear. The aim of this study was to investigate the effect of soluble cell adhesion molecules and some inflammatory markers on coronary plaque instability. The prospective study consisted of 15 patients with stable angina pectoris (SAP), 16 with unstable angina pectoris (UAP), and 16 who had undergone percutaneous transluminal coronary angioplasty (PTCA). Blood samples were obtained from the SAP group on admission, from the UAP group at the early stage of pain onset within 6 h of pain, and again after 12 h of pain. Samples from the PTCA group were collected before, 2, 14 h after the procedure. Soluble vascular cell adhesion molecule-1 (VCAM-1), endothelial selectin, interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2), and C-reactive protein (CRP) were analyzed by enzyme-linked immunosorbent assay. CRP serum levels gradually increased although IL-2 gradually decreased in patients with UAP and PTCA. In addition, VCAM-1 levels were sharply decreased after the PTCA procedure. However, this value returned back to the preprocedure levels 14 h after PTCA. Both CRP and IL-2 are directly involved in the triggering mechanisms of acute coronary events.
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PMID:The role of inflammation markers in triggering acute coronary events. 1452 Apr 83

To assess the in-hospital prognostic value of cellular adhesion molecules (CAMs), the levels of soluble CAMs were measured at admission in 114 patients with severe unstable angina. Patients with an eventful in-hospital course (death, nonfatal acute myocardial infarction, and recurrence of angina) had higher levels of soluble vascular cell adhesion molecule-1 than those without events (p = 0.01); this association was independent of classic risk factors and C-reactive protein.
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PMID:Usefulness of elevated levels of soluble vascular cell adhesion molecule-1 in predicting in-hospital prognosis in patients with unstable angina pectoris. 1460 95

Adhesion molecules play an important role in the development and course of coronary atherosclerosis. In this study, soluble forms of vascular cell adhesion molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were evaluated in patients with various clinical presentations of coronary atherosclerosis and compared them to those with angiographically documented normal coronary arteries. Venous plasma samples were collected from 43 patients with acute myocardial infarction (AMI), 45 with unstable angina pectoris (UAP), 34 with stable angina pectoris (SAP) and 29 subjects with normal coronary arteries (control). The VCAM-1 level was significantly higher in patients with AMI (mean +/- SEM; 799.8 +/- 26.3 ng/ml) than those with UAP (644.2 +/- 26.7 ng/ml) and SAP (526 +/- 32.5 ng/ml) and controls (270 +/- 26.8 ng/ml). In patients with UAP, VCAM-1 was found to be significantly elevated as compared to the SAP group and controls. VCAM-1 level was also higher in SAP group than the controls. Serum levels ICAM-1 were similar among patients with AMI (424.1 +/- 15.2 ng/ml), UAP (403 +/- 12.3 ng/ml) and SAP (381.2 +/- 16.2 ng/ml); however, levels of ICAM-1 was significantly elevated in these groups as compared to the controls (244.3 +/- 11). The mean level of E-selectin was not different in AMI and UAP groups (47.2 +/- 2.2 vs. 42.6 +/- 2.1 ng/ml; respectively). However, it was significantly higher in acute coronary syndrome groups as compared to SAP (33.4 +/- 2.3 ng/ml) and control subjects (30.7 +/- 1.9 ng/ml). Serum levels of E-selectin were similar in SAP group and controls. For P-selectin, no significant difference was observed between AMI and UAP groups (187.5 +/- 7.2 vs. 181.7 +/- 4.7 ng/ml; respectively), however, it was significantly higher in both groups as compared to SAP group (146.1 +/- 7.4 ng/ml) and controls (108 +/- 6.6 ng/ml). Serum level of P-selectin was significantly higher in patients with SAP than the control group. In conclusion, determination of serum VCAM-1, E-selectin and P-selectin levels seems more useful for detecting coronary plaque destabilization.
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PMID:Levels of soluble adhesion molecules in various clinical presentations of coronary atherosclerosis. 1526 39

It remains unclear what kind of morphologic and biochemical features best predict plaque rupture in patients with angina pectoris (AP). This study aimed to investigate whether combined high-frequency vascular ultrasound imaging and measurements of serum inflammatory biomarkers can predict coronary plaque ruptures in patients with AP. The study population consisted of 20 patients with stable AP and 40 patients with unstable AP. High-frequency vascular ultrasound imaging was performed in the 2 groups to measure intima-media thickness, the plaque acoustic density of the common carotid arteries, and the flow-mediated dilation of the brachial arteries. Serum lipid profile and inflammatory biomarkers were measured in all patients. Using intravascular ultrasound, a list of coronary imaging parameters was obtained. A multivariate logistic regression model was applied to calculate the odds ratio of each parameter to predict coronary plaque ruptures detected by intravascular ultrasound. Of 139 coronary artery plaques identified by intravascular ultrasound, 48 plaques (9 in stable AP and 39 in unstable AP) developed ruptures. Among measured parameters, the values of carotid intima-media thickness, coronary external elastic membrane area, plaque area, plaque burden, plaque eccentric index and remodeling index, serum high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly higher in unstable AP than in stable AP (p <0.05 to 0.01). Of these parameters, carotid intima-media thickness, serum high-sensitivity C-reactive protein, and the coronary remodeling index were found to be significant predictors of coronary plaque rupture, with odds ratios of 9.51 (95% confidence interval 1.29 to 21.81), 3.02 (95% confidence interval 1.01 to 7.65), and 0.01 (95% confidence interval 0.00 to 0.34), respectively. In conclusion, combined high-frequency ultrasound imaging of coronary and carotid arteries and measurements of serum inflammatory markers are able to predict coronary plaque ruptures in patients with AP.
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PMID:Usefulness of high-frequency vascular ultrasound imaging and serum inflammatory markers to predict plaque rupture in patients with stable and unstable angina pectoris. 1847 72


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