Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have clarified the significance of chemokines in cardiovascular diseases, such as development of atherosclerosis, atheromatous plaque rupture and restenosis after coronary angioplasty. We investigated changes in chemokine expression in the coronary circulation induced by percutaneous transluminal coronary angioplasty (PTCA) and their clinical significance. We examined 40 patients with angina pectoris who underwent elective PTCA for isolated stenotic lesions of the left coronary artery. Eight patients received PTCA only, 14 percutaneous transluminal rotational atherectomy and 18 stent implantation. Venous blood samples were obtained from the coronary sinus before, and immediately after as well as 4 and 24 h after PTCA. Plasma levels of interleukin (IL)-8, macrophage-colony stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP)-1 were measured by enzyme-linked immunosorbent assay. Plasma levels of M-CSF in the coronary sinus blood showed significant increases 4 and 24 h after PTCA. On the other hand, plasma MCP-1 levels did not change significantly during a 24-h observation period after PTCA. Immunoreactive IL-8 was not detected in any patients before or after PTCA. A significant positive correlation was found between plasma M-CSF levels 24 h after PTCA and late loss index 6 months after the procedure. Plasma levels of M-CSF 24 h after PTCA were significantly higher in patients with than in those without late restenosis. PTCA induced increases in plasma levels of M-CSF in the coronary circulation. Increased M-CSF expression may be involved in neointima formation at injured vessels through activation of mononuclear phagocytes.
 ...
PMID:Chemokine expression in coronary circulation after coronary angioplasty as a prognostic factor for restenosis. 1136 10

The levels of platelet-derived microparticles (PDMPs), platelet activation markers (P-selectin, CD63, and PAC-1 on activated platelets), and C-C chemokines (monocyte chemotactic peptide [MCP]-1 and regulated on activation normally T-cell expressed and secreted [RANTES] were measured and compared in patients with acute myocardial infarction (AMI) or stable pectoris angina. These substances are thought to paricipate in the development of complications in patients with AMI. The percentage binding of anti-P-selectin, CD63, and PAC-1 antibody to platelets, and the levels of PDMPs (per 10(4) platelets) were higher in the patients with AMI than in those with stable pectoris angina (P-selectin, 23.1% +/- 2.1% vs. 10.3% +/- 1.2%, p < 0.001; CD63, 24.6% +/- 3.3% vs. 11.2% +/- 3.1%, p < 0.01; PAC-1, 14.1% +/- 1.7% vs. 9.3% +/- 2.1%, p < 0.05; PDMPs, 613 +/- 71 vs. 413 +/- 55, p < 0.01). There were no differences in platelet levels of GPIIb/IIIa and GPIb between groups. Levels of MCP-1 and RANTES were higher in the patients with AMI than in patients with stable pectoris angina (MCP-1, 430 +/- 35 vs. 265 +/- 23, p<0.01; RANTES, 175 +/- 32 vs. 88 +/- 29, p<0.001). The effects of percutaneous transluminal coronary angioplasty (PTCA) on the levels of these agents in patients with AMI were studied. Platelet activation markers were significantly decreased in patients with AMI after PTCA. RANTES level was also significantly decreased after treatment, but MCP-1 level was not changed. In addition, this tendency was clearer in STENT patients. These findings suggest that in patients with AMI PTCA, particularly STENT, may prevent the development of complications in which activated platelet and RANTES participate.
 ...
PMID:Association of platelet-derived microparticles with C-C chemokines on vascular complication in patients with acute myocardial infarction. 1236 Dec 7

This study investigated whether the myocardium is involved in the acute inflammatory reaction associated with bursts of unstable angina (UA). We looked for the presence of activated DR+ inflammatory cells and the expression patterns, localization, and immunostaining identification of genes for cytokines (IL-1beta, TNF-alpha, IL-6, and IFN-gamma), MCP-1, and iNOS in the left ventricle biopsies from 2-vessel disease anginal patients, 24 with UA and 12 with stable angina (SA), who underwent coronary bypass surgery. Biopsy specimens from 6 patients with mitral stenosis who underwent valve replacement were examined as control hearts (CHs). Plasma levels of IL-2 soluble receptor (sIL-2R) were measured as a marker of systemic immune reaction. In CHs, DR+ cells were undetectable, and cytokine and iNOS mRNA expression were negligible. UA patients had higher sIL-2R levels than SA patients (P<0.01), and their biopsy specimens showed both numerous DR+ cells identified as lymphocytes, macrophages, endothelial cells, and elevated expression levels of cytokine and iNOS genes (from 2.4- to 6.1-fold vs SA; P<0.01). Cytokine and iNOS genes and proteins were localized in endothelial cells without involvement of myocytes. IL-1beta and MCP-1 mRNAs were nearly undetectable. No significant differences were found in the number of DR+ cells, levels of cytokine, and iNOS genes between potentially ischemic and nonischemic left ventricle areas. In SA specimens, DR+ cells were very rare and only mRNAs for TNF-alpha and iNOS genes were overexpressed versus CHs. These results indicated that an acute immunomediated inflammatory reaction, essentially involving coronary microvessels, is demonstrable in UA patients.
 ...
PMID:Immunomediated and ischemia-independent inflammation of coronary microvessels in unstable angina. 1277 81

Atherosclerosis is still an important disease. It accounts for 39% of deaths in the U.K. and 12 million U.S citizens have atherosclerosis-associated disease. Atherosclerosis may exert clinical effects by slow narrowing, producing stable angina or dramatic rupture, producing acute coronary syndromes such as unstable angina or myocardial infarction and death. Macrophages are abundant in ruptured atherosclerotic plaques. Macrophages are innate immune effectors, i.e. they are activated without antigenic specificity. This may make them liable to indiscriminate tissue damage, since they are less selective than lymphocytes. Macrophages are recruited and activated by many signals and have an impressive armamentarium of molecules to promote tissue damage. Macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (ICAM-1, VCAM, ELAM). Use of knockout mice has implicated the chemoattractant cytokine (chemokine) MCP-1 in attracting macrophage recruitment in atherosclerosis. Macrophage-activation stimuli associated with atherosclerotic risk factors include oxidised low density lipoprotein (oxLDL, "bad cholesterol"), advanced glycosylation end products (AGEs) of diabetes, angiotensin II and endothelin. Substantial work has clarified macrophage activation by OxLDL via macrophage scavenger receptors (MSRs), especially MSRA and CD36. Activated macrophages express effector molecules that kill cells and degrade extracellular matrix. These include Fas-L and nitric oxide (NO). Macrophage NO is derived from the high output inducible nitric oxide synthase (iNOS) pathway and upregulates vascular smooth muscle (VSMC) cell surface Fas, priming them for apoptosis. Activated macrophages express surface Fas-L, similar to cytotoxic T-lymphocytes and natural killer cells. Since VSMCs promote plaque stability, VSMC apoptosis may promote plaque rupture. Macrophages express multiple metalloproteinases (e.g. stromelysin) and serine proteases (e.g. urokinase) that degrade the extracellular matrix, weakening the plaque and making it rupture prone. Macrophages secrete numerous other effectors including reactive oxygen species, eicosanoids, tumour necrosis factor alpha and interleukin-1. Macrophage-derived transforming growth factor beta promotes fibrosis. Existing cardiovascular treatments including angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors, aspirin, cholesterol reduction agents especially statins may inhibit macrophages. The interaction of NO-donors with macrophages and apoptosis is complex and bifunctional. Traditional anti-inflammatory agents such as glucocorticoids and cyclophosphamide have very serious side effects and are probably inappropriate. Novel anti-inflammatory agents e.g. new immunosuppressives and anti-TNF therapy may have an improved cost-benefit ratio.
 ...
PMID:Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. 1563 83

The aim of our work was to find if MCP-1 -2518 (A/G) single nucleotide polymorphism (SNP) influences somehow the serum concentrations of high-sensitive CRP (hsCRP) both in patients suffering from ischemic heart disease (IHD), myocardial infarction (MI), angina pectoris (AP), and hypertension (HT) and in control group of healthy subjects. Totally, 263 patients with the diagnosis of IHD, out of them 89 with MI, 145 with AP, 205 with HT, and also 67 healthy subjects were included in the study. First, we estimated the serum levels of hsCRP. We found that patients with AP had significantly higher serum level of hsCRP than both control group of healthy subjects (P = .043) and IHD patients without AP (P = .026). The presence of the mutant G allele statistically significantly correlated with the higher serum levels of hsCRP in patients with IHD (P = .016), AP (P = .004), and HT (P = .013). Higher correlations were found in men (AP: P = .019; HT: P = .047). In all cases the highest levels of hsCRP were found both in patients and healthy controls with homozygous GG genotype.
 ...
PMID:Association of MCP-1 -2518 A/G single nucleotide polymorphism with the serum level of CRP in Slovak patients with ischemic heart disease, angina pectoris, and hypertension. 1963 50

Inflammation plays a pivotal role in coronary heart disease. Dendritic cells (DCs) are principal players in inflammation and atherosclerosis. Although the percentage of circulating DC precursors in coronary heart disease have been investigated, circulating myeloid DC (mDC) and plasmacytoid DC (pDC) precursors have not been extensively studied, particularly in relation to the severity of coronary artery lesions in patients with coronary heart disease. In this study, we recruited controls (n = 29), patients with stable angina pectoris (SAP, n = 30), patients with unstable angina pectoris (UAP, n = 56), and patients with acute myocardial infarction (AMI, n = 50). The severity and extent of coronary artery lesions was evaluated by Gensini score, following coronary angiograms. The percentage of circulating mDC and pDC precursors was determined by fluorescence-activated cell sorting (FACS). Plasma levels of MCP-1 and MMP-9, which correlate with atherosclerosis and DC migration, were also measured. The percentage of circulating mDC precursors was reduced in patients with AMI and UAP compared with control and SAP patients, respectively (p < 0.01 for AMI vs. SAP and Control, p < 0.05 for UAP vs. SAP and Control). The percentage of circulating pDC precursors was not significant changed. The levels of plasma MMP-9 and MCP-1 and Genisi score were all increased in patients with AMI and UAP, compared to control and SAP patients, respectively (p < 0.01 for AMI vs. SAP and control, p < 0.05 for UAP vs. SAP and control). Overall, the percentage of circulating mDC precursors was negatively correlated with MCP-1 (p < 0.001), MMP-9 (p < 0.001) and Genisi scores (p < 0.001). Genisi scores were positively correlated with the levels of MCP-1 (p < 0.001) and MMP-9 (p < 0.001). Our study suggested that the percentage of circulating mDC precursors is negatively correlated with the severity and extent of coronary artery lesions in patients with coronary heart disease.
 ...
PMID:A decrease in the percentage of circulating mDC precursors in patients with coronary heart disease: a relation to the severity and extent of coronary artery lesions? 2222 98

The aim of this study is to determine miR-22 expression levels in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and to investigate whether MCP-1 expression is regulated by miR-22. miR-22 expression in PBMCs from 60 CAD patients including stable angina pectoris (SAP) (n = 29), unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (NSTEMI) (n = 17), or ST-elevation MI (STEMI) (n = 14) and 20 non-CAD subjects by real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were employed to determine whether miR-22 binds to 3'UTR of MCP-1. miR-22 mimics and inhibitors were transfected into healthy PBMCs. MCP-1 mRNA and protein levels were determined by qRT-PCR and enzyme-linked immuno sorbent assay, respectively. The qRT-PCR results showed that miR-22 levels in PBMCs were decreased in CAD patients, and MCP-1 was augmented in CAD patients and was inversely correlated with miR-22 levels. The luciferase activity assays indicated that MCP-1 was a target of miR-22. Overexpression of miR-22 could significantly repress MCP-1 expression at both mRNA and protein levels in PBMCs, whereas inhibition of miR-22 showed the opposite effects. This study revealed that miR-22 is downregulated in PBMCs from patients with CAD and that miR-22 may participate in inflammatory response by targeting MCP-1, therefore contributing CAD.
...
PMID:miR-22 contributes to the pathogenesis of patients with coronary artery disease by targeting MCP-1: An observational study. 2753 67