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

Biosynthesis of apolipoprotein (apo) E has been previously demonstrated to be regulated in macrophages by intracellular free cholesterol levels as well as by macrophage activating factors. In this report, the regulation of apo E secretion by cytokines detected within atherosclerotic lesions has been investigated. Granulocyte macrophage-colony stimulating factor (GM-CSF) stimulated macrophages had a 3-5-fold reduction in apo E secretion, comparable to that observed for gamma interferon (IFN gamma), while tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) resulted in a 2-fold decrease. In contrast to the reduction in apo E secretion by these cytokines, transforming growth factor beta (TGF-beta) stimulated macrophages secreted 3-fold greater amounts of apo E than controls. The reduced secretion of apo E by GM-CSF was reversible, heat labile, dose dependent, maximal 48 h after cytokine exposure and was coincident with an increase in fibronectin secretion. The opposing effects of GM-CSF and TGF-beta on apo E secretion were consistent with similar changes detected in apo E mRNA levels. Cytokine effects on apo E secretion in cholesterol loaded macrophages were also investigated and found to be similar to the non-loaded cells with GM-CSF decreasing and TGF-beta increasing apo E secretion. The observed differences in apo E secretion did not correlate with any significant changes in either cellular cholesterol distribution in the non-cholesterol loaded macrophages or in basal ACAT activity. In addition to changes in apo E secretion, cytokine treated macrophages pulsed with [14C]oleate and acetylated LDL for 2-6 h had a 2-fold increase (GM-CSF) or decrease (TGF-beta) in cholesterol esterification. Therefore, GM-CSF and TGF-beta mediated changes in apo E secretion may occur through a mechanism independent of changes in cellular free cholesterol levels. These results suggest that cytokines expressed within an atheroma may play an important role in the modulation of macrophage mediated reverse cholesterol transport.
Atherosclerosis 1992 Oct
PMID:Cytokine regulation of macrophage apo E secretion: opposing effects of GM-CSF and TGF-beta. 146 52

Tumor necrosis factor-alpha (TNF-alpha) was demonstrated in human normal and atherosclerotic aorta, iliac and femoral arteries by immunohistochemistry using monoclonal and polyclonal antibodies. TNF was present in the cells of the arterial wall and as granular and diffuse extracellular deposits in the connective tissue matrix. Quantitative determinations of TNF by ELISA showed mean values of 21.7 +/- 0.7 ng/100 mg total extracted protein in normal intima, 38.2 +/- 0.5 in intimal thickenings, 25.5 +/- 1.1 in fibrous plaques and 16.8 +/- 0.2 ng/100 mg total extracted protein in media. Intimal thickenings presented the highest amounts of TNF with a statistically significant difference when compared to normal intima (P less than 0.05) and media (P less than 0.01). TNF-alpha concentrations in arterial eluates were about 200 times higher than in the corresponding serum samples. Western blotting analysis confirmed TNF-alpha eluted from the arterial wall to be about 17 kDa similar to human recombinant TNF-alpha. TNF-alpha in human atherosclerotic wall could be actively involved in the inflammatory events associated with atherosclerosis.
Atherosclerosis 1991 Aug
PMID:Tumor necrosis factor-alpha in human arterial wall with atherosclerosis. 179 52

At present, it is known that the immune system acts through the release of protein factors, so-called cytokines. In addition to their immunomodulating and endocrinometabolic effects, cytokines have appeared to be able to have an influence on the cardiovascular system by inducing important haemodynamic changes. Cytokines cause hypotension, particularly IL-2 and TNF, due at least in part to a production of nitric oxide by endothelial cells. Cytokines, such as IL-1, IL-6 and TNF, stimulate myocardial infiltration by activating leukocytes and inducing the release of cytotoxic factors during myocardial infarction; that would extend the area of necrosis. Finally, cytokines would be involved in the pathogenesis of the atherosclerosis, and cholesterol metabolism itself would be under a cytokine control. On these bases, it is possible to suggest in the near future the elaboration of new therapeutic strategies and prognostic indications, according to the bioimmunological response of patients with cardiovascular diseases.
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PMID:[Cardioangioimmunology: the immune implications in the principle cardiovascular pathologies]. 180 53

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.
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PMID:Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. 189 66

Copper-oxidized LDL has many of the characteristics of the modified LDL generated in the artery wall during the initial stages of atherosclerosis. It is not, however, a chemically defined species but shows significant variations in both its chemical composition and behaviour in biological systems depending upon the extent to which the peroxidation reaction has occurred (Fig. 1). Taking care to define the extent of LDL modification we have used this form of oxidized LDL to investigate the effects on the macrophage of this potentially toxic particle. This cell, in contrast to endothelial cells, appears to be particularly well adapted to detoxify lipid peroxidation products since it possesses glutathione peroxidases capable of metabolizing oxidized LDL and responds to oxidized LDL by increasing its GSH content. Acetylated LDL had little or no effect on GSH levels showing that lipid loading per se or recognition by the macrophage scavenger receptor is not sufficient to induce the synthesis of this antioxidant. We have confirmed the observation that oxidized LDL does not activate expression of the gene for TNF and raise the possibility that PGE2 produced by the cells and possibly during the oxidation of LDL may be the mediator suppressing the synthesis of this cytokine. Our results support the hypothesis that the lipid-laden macrophage does not contribute to an inflammatory response in the artery wall and imply a protective role for the macrophage in scavenging oxidized LDL.
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PMID:Oxidation of low-density lipoprotein and macrophage derived foam cells. 208 7

Monocytes and endothelial cell interactions play a key role in the development of vascular lesion, inflammation and atherosclerosis. Leukocyte adhesion is mediated through specific molecules CD11/CD18 complexes on the leukocyte side and the ELAM (Leukocyte Adhesion Molecule) ICAM (Intercellular Adhesion Molecule) on the endothelium cell surface. Several monocyte products damage endothelial cells such as free radicals, oxygen peroxides, proteases, hydrolases, lipases... Various monokines alter endothelial cell function and proliferation. Interleukin 1, gamma interferon, alpha tumor necrosis factor increase ELAM, further more they induce the synthesis of procoagulant activity by endothelial cells. Monocyte derived growth factor stimulates endothelial cells proliferation while transforming growth factors, beta (TGF beta) and TNF alpha inhibit endothelial cell growth. Lipid products of monocyte origins such as leukotrienes induce an activation of endothelial cells which results in a production of prostacyclin. Monocytes may also participate in the coagulation process by producing thromboplastin and coagulation factors and facilitating the tenase (activation of factor X) complex formation. On the other hand, monocyte also synthesize tissue plasminogen activator and inhibitor. The numerous factor produced by monocytes may affect in different ways the endothelial cell behavior.
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PMID:[Monocyte-endothelium relations]. 265 10

Pentoxifylline has been used for several years in various types of peripheral and cerebrovascular diseases because of its hemorheological properties: pentoxifylline improves the red cell deformability, decreases platelet and red cell aggregation, decreases fibrinogen and plasma viscosity. Its new properties on the leukocyte function can lead to new therapeutical ways. Adherence and peroxidative free radicals production are induced by inflammatory cytokines (IL1, TNF) and can induce vascular tissue damages and development of atherosclerosis. Pentoxifylline has no effect on the normal leukocyte function. However, in all inflammatory diseases, Pentoxifylline acts on the activated neutrophil function: Pentoxifylline decreases adherence to endothelial cells or other surfaces, the superoxide and lysozyme release, and increases chemotaxis. In some animal models of shock and infection, pentoxifylline decreases cellular and tissue damages, mediated by activated neutrophils. Furthermore, in inhibiting neutrophil adhesion to cultured endothelium cells, pentoxifylline, modulates leukocyte-endothelium and leukocyte-platelets interactions which are important factors in the development of inflammation and thrombosis. Pentoxifylline increases the leukocytes mediated activation of fibrinolytic pathways and could play an important role in the prevention of thrombosis. In addition to its well-known effects on chronic vascular diseases, pentoxifylline is also effective in some acute injuries in animal models. This can lead to new research fields allowing a better understanding of atheromatous processes.
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PMID:[New aspects of the pharmacology of pentoxifylline]. 265 14

The social importance of endocrinology is apparent from an analysis of the prevalence of endocrinopathies in the CSSR. They affect (incl. diabetes and eufunctional goitre) some 10% of the population. The author submits a brief account of the development of knowledge of hormones and of Nobel prizes awarded for hormone research. On some examples he demonstrates the importance of endocrinology for other medical disciplines: the interrelationship of stress and infectious reactions via interleukin 1, the discovery of a series of new growth and immune factors; the participation TNF (cachectin, tumour necrosis factor) in pathological processes (tumours, atherosclerosis); vasoactive peptides EDRF (endothelium derived relaxation factor), endothelin (vasoconstriction), GM-CSF (granulocyte-macrophage colony stimulating factor) in treatment of radiation sickness and adjuvans in chemotherapy; interleukins. These new peptide hormones are words in the complex cellular signal alphabet the importance of which in the control of cellular activities we are beginning to understand.
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PMID:[Endocrinology: lessons from the past, hopes for the future]. 271 85

The procoagulant response of endothelium to pathophysiological agents such as tumour necrosis factor alpha (TNF alpha) and phorbol myristate acetate (PMA) alters the expression of proteins such as tissue factor. The modulation of such procoagulant activity (PCA) by the polyunsaturated fatty acid arachidonic acid (20:4,n-6) and its 15-hydroperoxy (15-HPETE) and 15-hydroxy (15-HETE) metabolites was examined since this may have important implications in cardiovascular disease and atherosclerosis. Treatment of human umbilical vein endothelial cells (HUVEC) for 30 min with 20:4, 15-HPETE or 15-HETE before induction of PCA with TNF alpha (100 U) or PMA (10(-7) M) caused a significant inhibition of PCA. This inhibition was seen at 2-5 microM fatty acids. Dose response curves with TNF alpha indicated that the inhibition was greatest at higher concentrations of TNF alpha (> or = 250U TNF alpha/ml). The mode of administration of the fatty acid was not critical as fatty acids presented as DPC-fatty acid micelles or solubilised in ethanol gave similar inhibitions of PCA. 20:4, 15-HPETE or 15-HETE did not alter the binding of I125-labelled TNF alpha to its surface receptors on HUVEC, suggesting that the effect of these fatty acids was not mediated by events at the cell surface receptor level. In support of this, these fatty acids were found to inhibit PCA induced by PMA which bypasses cell surface receptors to activate protein kinase C directly.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1995 Jul
PMID:Inhibitory effects of arachidonic acid (20:4,n-6) and its monohydroperoxy- and hydroxy-metabolites on procoagulant activity in endothelial cells. 748 27

Early features in the pathogenesis of atherosclerosis include accumulation of oxidized LDL (oxLDL) and endothelial expression of the vascular adhesion molecule VCAM-1. Because antioxidants inhibit endothelial VCAM-1 expression, we tested the hypothesis that oxLDL functions as a prooxidant signal in atherogenesis to augment VCAM-1 activation by inflammatory signals. Cultured human aortic endothelial cells (HAECs) or human umbilical vein endothelial cells (HUVECs) were incubated with unmodified LDL, oxLDL, or glycated LDL for 48 h. No change in VCAM-1, intercellular cell adhesion molecule-1 (ICAM-1), or E-selectin expression from control was observed by ELISA. However, dose-response and time course studies demonstrated that oxLDL enhanced VCAM-1 expression induced by the cytokin tumor necrosis factor alpha (TNF alpha) 63% in HAECs and 45% in HUVECs over unmodified LDL or control. Using flow cytometry analysis, oxLDL augmented TNF alpha-induced VCAM-1 expression in a uniform HAEC population. oxLDL had no effect on E-selection induction. oxLDL augmented TNF alpha-induced ICAM-1 expression 44% in HAECs but not in HUVECs. Glycated LDL augmented TNF alpha-induced VCAM-1 expression 35% in HAECs but not HUVECs. Similar results were obtained with 13-HPODE or lysophosphatidylcholine, significant components of oxLDL. 13-HPODE augmented TNF alpha-induced mRNA accumulation and transcriptional activation of VCAM-1 in HAECs. These results suggest that as long-term regulatory signals, specific oxidized fatty acid and phospholipid components of oxLDL augment the ability of vascular endothelial cells to express cytokine-mediated VCAM-1. These studies link oxidant signals conferred by oxLDL to oxidation-sensitive regulatory mechanisms controlling the expression of endothelial cell adhesion molecules involved in early atherosclerosis.
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PMID:Modified low density lipoprotein and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells. 753 87


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