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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular immunity may play a role in the pathogenesis of atherosclerosis. In this report the potential role of these cells in the formation of abdominal aortic aneurysms by immunohistochemistry was investigated. Aortic tissues from 32 patients were examined: 4 normal aortas, 6 aortas with occlusive atherosclerotic disease, 17 abdominal aortic aneurysms, and 5 inflammatory abdominal aneurysms. Using monoclonal anti-CD3 (T cells), anti-CD19 (B cells), anti-CD11c (macrophages), anti-CD4 (T helper cells), and anti-CD8 (T suppressor cells), several distinctions among these groups were found. The amount of inflammatory cell infiltrate was as follows: inflammatory aneurysms more than abdominal aortic aneurysms more than occlusive aortas more than normal aortas. CD3-positive T lymphocytes rarely were found in the adventitia of normal or occlusive aortas. In contrast, abdominal aortic aneurysms and inflammatory aneurysms exhibited most of the CD3-positive infiltrates in the adventitia. CD19-positive B lymphocytes were present mainly in the adventitia of all pathologic tissues. The CD4-positive:CD8-positive ratio was greater in abdominal aortic aneurysms and inflammatory aneurysms than in the other groups, both in the adventitia and in the media of the aortas. CD11c-positive macrophages were present throughout the diseased tissues, often surrounded by lymphoid aggregates; the greatest numbers of macrophages were found in the inflammatory aneurysm group. Our data suggests that the aneurysmal disease may progress from occlusive disease and is accompanied by an increase in chronic inflammatory cells as well as a redistribution of these cell types. Therefore it is suggested that aneurysmal disease may represent an immune-mediated event.
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PMID:Human abdominal aortic aneurysms. Immunophenotypic analysis suggesting an immune-mediated response. 170 Jun 20

Seven cases of inflammatory abdominal aortic aneurysms (IAs) were studied by light microscopy, transmission electron microscopy (TEM) and immunohistochemistry. Microscopically, atherosclerosis coexisted with adventitial fibrosis and inflammation. The inflammatory component showed a follicular and a diffuse pattern. Fibrous entrapment of fatty tissue, adventitial vasculitis, neuritis were also common findings. By TEM, sparse smooth muscle cells having dilated cisternae of rough endoplasmic reticulum, large bundles of collagen fibres and oedematous, amorphous fibrillary elastin were observed. By immunohistochemistry, the follicles mostly contained CD22+ B-cells. T4- (CD2+/CD4+/CD8-), T8-(CD2+/CD4-/CD8+) cells as well as macrophages (CD4+/CD11c+) and follicular dendritic reticulum cells (DRC1+) were also detected. The monoclonal antibody Ki-67 reacted with 2-48% of germinal center cells. In the fibrous extrafollicular adventitia, actively synthesizing plasma cells prevailed over T4-cells, and macrophages. Some of the macrophages were also activated (CD4+/CD11c+/CD25+/CD30-). IgM, IgG and C3c deposits were detected in the fibrous zone, in the germinal centers, within adventitial vessels and nerves. HLA-DR antigen was diffusely expressed in cells populating both the fibrous and the follicular zones as well as in endothelial and Schwann cells. These findings suggest that IAs could develop in some individuals affected by advanced atherosclerosis of the abdominal aorta through a pathogenic B-cell response to locally presented antigens.
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PMID:An immunohistochemical study of inflammatory abdominal aortic aneurysms. 809 31

To assess the numeric and functional changes in circulating white blood cells in the presence of severe atherosclerosis, 25 subjects with marked, angiographically assessed, atherosclerotic lesions and 29 selected controls were studied. Of the differential leukocyte counts, only monocyte count was significantly higher in the atherosclerotic than in the control subjects (449.0 +/- 115.6 (1 S.D.) vs. 344.1 +/- 138.8/mmc; P = 0.0016). By flow-cytometry no significant differences concerning monocyte surface antigens were found, except a feeble decrease in beta 2-microglobulin in the atherosclerotic subjects. As to lymphocytes, an increase in the CD8 population (33.4 +/- 6.8 vs 28.6 +/- 6.5%; P = 0.0144) and decreases in class I HLA antigen (96.6 +/- 7.3 vs 99.4 +/- 0.7%; P = 0.0049), beta 2-microglobulin (97.9 +/- 2.1 vs 99.3 +/- 1.0%; P = 0.0055) and especially in vivo DNA synthesis (3.8 +/- 1.2 vs 5.3 +/- 2.1%; P = 0.0102) percent expressions were found in the atherosclerotic patients with respect to the controls. This study shows that circulating monocytes are increased in atherosclerotic disease, possibly due to their participation in the phagocytosis of lipids in the arterial wall, with no further immunologic involvement. Conversely, the replicative activity of T lymphocytes is decreased, which might be a consequence of or a factor predisposing to atherosclerosis.
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PMID:Immunologic changes in circulating leukocytes in the presence of atherosclerotic disease. 818 98

The aim of this study was to determine blood lymphocyte T subset counts in children with elevated levels of low-density lipoprotein cholesterol. We studied 107 children, ages 2.0 to 15.9 years, from 79 families who were referred to our Lipid Research Clinic because total cholesterol serum levels higher than 200 mg/dl had been detected in at least one child. At the time of diagnosis we analyzed serum lipoprotein profile and blood lymphocyte T subsets (CD3, CD4 and CD8). Children were classified according to LDL-C levels into three groups: (1) normal, if levels were between the 5th and 75th percentiles (50 and 125 mg/dl, respectively); (2) at moderate risk, if levels were between the 75th and 95th percentiles (125 and 150 mg/dl, respectively); and (3) at high risk, if levels were above the 95th percentile (150 mg/dl). In children aged 2.0 to 6.9 years, all lymphocyte T subset counts were higher in the high risk group than in the normal group (P < 0.05 and P < 0.01). In children aged 11.0 to 15.9 years, the CD4 subset count was also significantly higher in the high risk group in the other two groups (P < 0.05 and P < 0.01). These results are in agreement with pathologic findings in the atheromatous plaque.
Atherosclerosis 1995 Sep
PMID:Lymphocyte T subset counts in children with elevated low-density lipoprotein cholesterol levels. 854 48

Coronary plaque inflammation may promote plaque rupture and thrombosis. To test this hypothesis, 351 coronary plaques from 83 patients were formalin-fixed and stained with haematoxylin and eosin. There were six groups: (1) ruptured plaques; (2) intact plaques from recently infarcted hearts; (3) plaques from hearts with severe coronary atherosclerosis without identifiable thrombosis; (4) native explanted hearts with severe coronary atherosclerosis; (5) cardiac transplant atherosclerosis; and (6) fatalities unrelated to coronary atherosclerosis. Selected arteries were immunostained for leukocyte markers and serially sectioned to identify plaque rupture. There were infiltrates of CD68-positive macrophages and CD3- and CD8-positive T cells adjacent to all plaque ruptures. Labelling with HLA-DR and CD30 indicated inflammatory cell activation. Plaque rupture was strongly statistically associated with the severity and frequency of superficial plaque inflammation but not that of deep plaque inflammation. Although atherosclerotic inflammation has been identified adjacent to rupture, this is its first comparison with control plaques. These results support the concept that inflammation in the fibrous cap is particularly associated with plaque rupture.
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PMID:Association of coronary plaque rupture and atherosclerotic inflammation. 907 9

The early colocalization of T cells and the potent immunostimulatory cytokine IFN-gamma to atherosclerotic lesions suggest that the immune system contributes to atherogenesis. Since mice with a targeted disruption of the apoE gene (apoE 0 mice) develop profound atherosclerosis, we examined the role of IFN-gamma in this process. First, the presence of CD4(+) and CD8(+) cells, which secrete lesional IFN-gamma, was documented in apoE 0 atheromata. Then, the apoE 0 mice were crossed with IFN-gamma receptor (IFNgammaR) 0 mice to generate apoE 0/IFNgammaR 0 mice. Compared to the apoE 0 mice, the compound knock-out mice exhibited a substantial reduction in atherosclerotic lesion size, a 60% reduction in lesion lipid accumulation, a decrease in lesion cellularity, but a marked increase in lesion collagen content. Evaluation of the plasma lipoproteins showed that the compound knockout mice had a marked increase in potentially atheroprotective phospholipid/apoA-IV rich particles as well. This correlated with an induction of hepatic apoA-IV transcripts. These observations suggest that IFN-gamma promotes and modifies atherosclerosis through both local effects in the arterial wall as well as a systemic effect on plasma lipoproteins. Therefore, therapeutic inhibition of IFN-gamma signaling may lead to the formation of more lipid-poor and stable atheromata.
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PMID:IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. 916 6

Sphingolipids and their metabolic products are now known to have second-messenger functions in a variety of cellular signaling pathways. Lactosylceramide (LacCer), a glycosphingolipid (GSL) present in vascular cells such as endothelial cells, smooth muscle cells, macrophages, neutrophils, platelets, and monocytes, contributes to atherosclerosis. Large amounts of LacCer accumulate in fatty streaks, intimal plaque, and calcified intimal plaque, along with oxidized low density lipoproteins (Ox-LDLs), growth factors, and proinflammatory cytokines. A possible role for LacCer in vascular cell biology was suggested when this GSL was found to stimulate the proliferation in vitro of aortic smooth muscle cells (ASMCs). A further link of LacCer in atherosclerosis was uncovered by the finding that Ox-LDLs stimulated specifically the biosynthesis of LacCer. Ox-LDL-stimulated endogenous synthesis of LacCer by activation of UDP-Gal:GlcCer,beta1-4galtransferase (GalT-2) is an early step in this signaling pathway. In turn, LacCer serves as a lipid second messenger that orchestrates a signal transduction pathway, ultimately leading to cell proliferation. This signaling pathway includes LacCer-mediated activation of NADPH oxidase that produces superoxide. Such superoxide molecules stimulate the GTP loading of p21(ras). Subsequently, the kinase cascade (Raf-1, Mek2, and p44MAPK [mitogen-activated protein kinase]) is activated. The phosphorylated form of p44MAPK translocates from the cytoplasm to the nucleus and engages in c-fos expression, proliferating cell nuclear antigen (PCNA) such as cyclin activation, and cell proliferation takes place. Interestingly, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of GalT-2, can abrogate the Ox-LDL-mediated activation of GalT-2, the signal kinase cascade noted above, as well as cell proliferation. Additional studies have revealed that LacCer mediates the tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappaB expression and intercellular adhesion molecule (ICAM-1) expression in vascular endothelial cells via the redox-dependent transcriptional pathway. LacCer also stimulates the expression of CD11/CD8, or Mac-1, on the surface of human neutrophils. Collectively, this phenomenon may contribute to the adhesion of neutrophils or monocytes to the endothelial cell surface and thus initiate the process of atherosclerosis. In addition, the LacCer-mediated proliferation of ASMCs may contribute to the progression of atherosclerosis. On the other hand, programmed cell death (apoptosis) by proinflammatory cytokines such as TNF-alpha, interleukin-1, and high concentrations of Ox-LDL occur via activation of a cell membrane-associated neutral sphingomyelinase (N-SMase). N-SMase hydrolyzes sphingomyelin into ceramide and phosphocholine. In turn, ceramide or a homologue serves as an important stress-signaling molecule. Interestingly, an antibody against N-SMase can abrogate Ox-LDL- and TNF-alpha-induced apoptosis and therefore may be useful for in vivo studies of apoptosis in experimental animals. Because plaque stability is an integral aspect of atherosclerosis management, activation of N-SMase and subsequent apoptosis may be vital events in the onset of plaque rupture, stroke, or heart failure. Interestingly, in human liver cells, N-SMase action mediates the TNF-alpha-induced maturation of the sterol regulatory-element binding protein. Moreover, a cell-permeable ceramide can reconstitute the phenomenon above in a sterol-independent fashion. Such findings may provide new avenues for therapy for patients with atherosclerosis. The findings described here indicate an important role for sphingolipids in vascular biology and provide an exciting opportunity for further research in vascular disease and atherosclerosis.
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PMID:Sphingolipids in atherosclerosis and vascular biology. 976 22

Malignant lymphoma infiltrating the abdominal aorta and resulting in an aortic aneurysm has never been documented. We report here a case of angiocentric T-cell lymphoma in a 33-year-old man who for months presented intermittent fever, splenomegaly, and an abdominal pulsatile mass. Angiography revealed extensive aneurysmal dilatation of the infrarenal abdominal aorta, bilateral iliac artery, and right common femoral artery. Splenic abscess and infected abdominal aortic aneurysm were initially suspected. An urgent splenectomy and aneurysmectomy with an aortic bifemoral bypass were performed. Pathological examination of the aortic aneurysm showed extensive necrosis, severe atherosclerosis, and lymphoma cell infiltration of the aortic wall. The lymphoid cells in the aorta and spleen were stained positive for CD45RO, CD56, and CD8, but negative for CD4 and CD19. Double-labeling immunohistochemistry and in situ hybridization using EBER1 for Epstein-Barr virus (EBV) revealed positive nuclear staining in the atypical T-lymphoid cells. This is the first definitive proof of peripheral T-cell lymphoma involving the abdominal aorta. Our evidence also supports that the EBV infection of T cells could be responsible for the atherosclerosis and hypertriglyceridemia, and the angiocentricity of the tumor cells apparently results in the presenting atherosclerotic aortic wall destruction, providing an additional causative concept for abdominal aortic aneurysm.
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PMID:Epstein-Barr virus-containing T-cell lymphoma and atherosclerotic abdominal aortic aneurysm in a young adult. 1049 49

A line of Japanese quail selected for high plasma cholesterol is highly susceptible to diet-induced atherosclerosis. Lymphocyte epitopes recognized by mouse anti-chicken monoclonal antibodies (c-mAb), TCR-1, TCR-2, TCR-3. CD-3, CD-4, CD-8, and BU-1a/b were reacted with spleens from quail selected for high (HL) and low (LL) plasma total cholesterol and their nonselected controls (CL). Cross reactivity to c-mAb and effect of line and gender were immunohistochemically evaluated. Chicken spleens were positive controls. Quail were immunologically stimulated with either sheep red blood cells (SRBC) or Brucella abortus 2 weeks before spleens were removed. Quail spleen epitopes of all lines recognized TCR-3 and CD-8 c-mAb, but no other c-mAb. Number of reacting cells and staining intensity to the TCR-3 c-mAb were greater in the HL than in the LL regardless of the stimulating Ag or dose used. For the CD-8 c-mAb, there were no differences among lines in birds receiving SRBC. In B. abortus-immunized birds, sex x line interactions indicated that males of the HL and CL had lower responses than females but LL males were not different than females. TCR-3 and CD8 c-mAb may be useful in studying immunological mechanisms for atherosclerosis in Japanese quail.
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PMID:Epitopes for chicken monoclonal antibodies in spleens of selected Japanese quail lines. 1051 60

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.
Atherosclerosis 2000 Apr
PMID:Relation of inflammation to vascular function in patients with coronary heart disease. 1072 91


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