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)

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

While T helper cell infiltration is an early event in the development of atherosclerosis in cholesterol-fed rabbits, their functional contribution to atherogenesis is not clear. To investigate their role, T cell activation was blocked with cyclosporine A (CsA) in New Zealand White (NZW) rabbits fed a 1% cholesterol diet. CsA was administered at a dose of 16 mg/kg body weight, intramuscularly every second day, resulting in circulating whole blood levels of 460 +/- 39 micrograms/l. After 4 weeks on the cholesterol diet, untreated rabbits developed atherosclerotic plaques covering 74.4% +/- 3.5% of their aortic arch, 19.8% +/- 7.8% of their thoracic aorta and 19.8% +/- 6.2% of their abdominal aorta. T cells were observed in plaques of their aortic arches (CD5 positive, 11.1 +/- 7.3 cells/mm2; CD4 positive, 9.9 +/- 4.9 cells/mm2) by immunofluorescence using monoclonal anti-rabbit CD5 and CD4 antibodies. Rabbits treated with CsA developed significantly less extensive plaques after 4 weeks (aortic arch 33.0% +/- 6.2%, P < 0.001; thoracic aorta 6.3% +/- 1.5%, P < 0.05; abdominal aorta 2.7% +/- 0.5%, P < 0.005) than untreated rabbits. No CD4 or CD5 positive cells were observed in their plaques. Treatment with CsA did not affect the weight gain of rabbits or reduce their serum cholesterol levels. Circulating T cell numbers and subsets were unaffected. These studies suggest that inhibition of T cell activation prevents their localisation in plaques and reduces the extent of early lesions, suggesting a role for T cells in the initiation of atherosclerosis.
Atherosclerosis 1995 Aug
PMID:Cyclosporine treatment reduces early atherosclerosis in the cholesterol-fed rabbit. 757 73

The involvement of T cells in the early cellular events in atherosclerosis was studied in rabbits fed a 1% cholesterol diet by use of specific monoclonal anti-rabbit CD5 and CD4 antibodies. T cells were not seen in the aortic intimas of rabbits not fed cholesterol but were seen in intimal lesions in cholesterol-fed rabbits. Accumulation of T cells in plaques occurred between 2 and 4 weeks after commencement of cholesterol feeding, and the greatest density of CD5-positive T cells were observed after 4 weeks (11.2 +/- 6.0 cells/mm2 [mean +/- SEM]; P < .02 compared with normal control rabbits, P < .03 compared with 2-week plaques). Staining for CD4 indicated that the majority of these T cells were T helper cells (9.9 +/- 4.9 cells/mm2). At this time, plaques showed a dense cellular infiltrate of macrophages (3623 +/- 467 cells/mm2) and macrophage proliferation was evident (2.1 +/- 1.1% of total plaque cells). As the cross-sectional area of intimal lesions increased progressively in subsequent weeks, their cellularity declined (8 weeks, 2239 +/- 271 cells/mm2; 12 weeks, 1535 +/- 55 cells/mm2; 16 weeks, 1747 +/- 242 cells/mm2, P < .05 for all groups compared with the 4-week group). The density of the T cell infiltrate (8 weeks, 6.7 +/- 3.0 cells/mm2; 12 weeks, 0.6 +/- 0.2 cells/mm2; 16 weeks, 1.0 +/- 0.4 cells/mm2) and the proliferative index of cells within plaques (8 weeks, 0.6 +/- 0.2%; 12 weeks, 0.8 +/- 0.3%; 16 weeks, 0.2 +/- 0.2%) also declined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:T helper cell infiltration and foam cell proliferation are early events in the development of atherosclerosis in cholesterol-fed rabbits. 758 28

"Lipo-PGE1", PGE1 incorporated into lipid microspheres (LM), has marked antiplatelet and vasodilatory actions. Since LM largely accumulate in inflamed vascular lesions, lipo-PGE1 shows a marked efficacy for treating vascular diseases such as atherosclerosis and vasculitis. Another recently developed drugs against intractable vasculitis are monoclonal antibodies to surface antigens of lymphocytes. Treatment with humanized anti-CDw52, and subsequent anti-CD4 monoclonal antibodies was reported to have brought remission up to 42 months.
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PMID:[Development of new drugs for intractable vasculitis--lipo-PGE1 and monoclonal antibody]. 793 10

T lymphocytes and macrophages (M phi) have been seen to accumulate at sites of lesions in blood vessel walls, suggesting that these cells may contribute to the pathogenesis of inflammatory reactions. Tumour necrosis factor-alpha (TNF-alpha), a cytokine produced by both M phi and T lymphocytes, plays a major role in inflammatory reactions, blood vessel formation, thrombosis and atherosclerosis. We now report that secretion of TNF-alpha by cloned CD4+ rat T cells, and to a lesser degree by peripheral T cells, and M phi can be induced in vitro in the absence of antigen, in a major histocompatibility complex (MHC) class II-independent manner by integrin-mediated recognition of immobilized components of extracellular matrix such as fibronectin and laminin; the secretion of TNF-alpha by the interacting resting cells on fibronectin was partially abrogated by the presence of the Arg-Gly-Asp (RGD)-containing amino acid sequence. This T cell-M phi interaction involves CD2 and CD4 molecules and requires a signal transduced in the T cells by a protein tyrosine kinase. Thus, a multicellular interaction with extracellular matrix protein exposed as a consequence of vascular wall injury can serve to signal the secretion of TNF-alpha which induces the recruitment of additional immune cells to the developing lesion.
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PMID:Extracellular matrix induces tumour necrosis factor-alpha secretion by an interaction between resting rat CD4+ T cells and macrophages. 809 10

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

Probucol is a clinically important drug that decreases plasma cholesterol in humans and has a marked anti-atherogenic effect in hyperlipidaemic Watanabe rabbits. The action of probucol in this animal model has been partly attributed to its anti-oxidant abilities. Probucol can decrease the oxidative modification of low-density lipoprotein and hence diminish its uptake by macrophages. In this paper, we have examined the effect of probucol on the monoblastic cell line U937 and on U937 cells induced to differentiate towards a macrophage phenotype by 1,25-dihydroxycholecalciferol (DHCC), tumour necrosis factor-alpha (TNF-alpha) or phorbol myristate acetate (PMA). We found that probucol enhanced the proliferation of undifferentiated U937 cells. Probucol also enhanced proliferation in cultures that had been pre-treated with DHCC or TNF-alpha, but had no effect on cultures that had been pre-treated with PMA. In contrast, when U937 cells were treated simultaneously with probucol and DHCC or TNF-alpha, there was a more marked decrease in proliferation than was induced by these agents in the absence of probucol. Probucol had little effect on the phenotype of resultant cells. The surface expression of CD13 (aminopeptidase N), CD4, CD35 (C3b receptor), CD64 (Fc gamma RI), CD71 (transferrin receptor) and HLA Class II was not affected by probucol. Probucol treatment led to a small increase in the surface expression of CD16 (Fc gamma RIII) in TNF-alpha treated cells and to a small decrease in the expression of CD14 (a monocyte marker) in PMA-treated cells. The induction of c-fgr mRNA and TNF-alpha mRNA by DHCC or PMA or TNF-alpha was not significantly altered in the presence of probucol. The affect of probucol on U937 cells does not appear to be due to its anti-oxidant abilities because butylated hydroxytoluene (BHT), an equally powerful anti-oxidant, did not have the same effect on the cell proliferation as probucol and because no changes were detected in the levels of lipid peroxidation in U937 cell culture supernatants.
Atherosclerosis 1993 Feb
PMID:Effects of the synthetic anti-oxidant, probucol, on the U937 monoblastoid cell line. 846 Oct 53

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

Atherosclerosis has been reported in some HIV-positive subjects without any known risk factor. The purpose of the present study was to investigate cervical arteries, abdominal aorta and femoral arteries by B-mode ultrasonography and doppler in 30 HIV-positive subjects matched to 18 controls for sex, age, tobacco consumption and arterial hypertension. Although no haemodynamically or clinically relevant lesions were found, plaques occurred more often in patients than in controls (11 patients, 36.7% vs. 2, 11.1%; P = 0.05). Compared to the HIV-positive patients without plaques, those with plaques had a tendency to have decreased lower HDL cholesterol, higher tobacco consumption and lower CD4-cell count (77 +/- 85/mm3 vs. 220 +/- 202/mm3). The patients with plaques (but not those without plaques) had lower HDL cholesterol than controls (P = 0.03). Asymptomatic atherosclerosis seems to be more frequent in HIV-positive patients and is associated to lower HDL cholesterol.
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PMID:Asymptomatic atherosclerosis in HIV-positive patients: A case-control ultrasound study. 865 49

It has been suggested that immune responses are involved in the development of atherosclerosis. We have evaluated this possibility by analyzing immunocompetent cells in a murine model of the disease. Apolipoprotein E knockout (apoE -/-) mice are genetically hypercholesterolemic due to targeted disruption of the apolipoprotein E gene and develop severe atherosclerosis. Such mice were fed either standard pellets or a diet containing 1.25% cholesterol. Lesions were analyzed from mice at 9 and 16 weeks of age. Immunohistochemical staining of fatty streaks showed that CD4+ T cells were frequent, both in clusters and as single cells. In advanced atherosclerotic plaques, CD4+ T cells were prominent in the fibrous cap and subendotbelially, whereas CD8+ T cells were sparse. The CD25 subunit of the interleukin-2 receptor, which is a marker for activated T cells, was expressed in CD4-rich areas and the major histocompatibility complex class II antigen, I-A(b), which is induced by cytokines released from activated T cells, was also found in the lesions. These data indicate that CD4+ T cells participate in the formation of atherosclerotic lesions in genetically hypercholesterolemic apoE -/- mice. They suggest that immune activation is part of the disease process, and we speculate that a direct link may exist between cholesterol accumulation and T cell activation, possibly by autoimmune responses to modified lipoproteins.
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PMID:Evidence for a local immune response in atherosclerosis. CD4+ T cells infiltrate lesions of apolipoprotein-E-deficient mice. 870 75


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