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)

Ischemic optic neuropathy and retinal arterial occlusion are 2 forms of arterial occlusive disease affecting the eye. Reports in the literature suggest platelet hyperactivity in acute arterial occlusive diseases affecting other organ systems. Therefore, 14 patients with ischemic optic neuropathy and 17 patients with central or branch retinal artery occlusion were studied to determine whether platelets have a role in the pathogenesis of these vascular occlusive disorders. The results of the following investigations were no different in these patients compared with those in 18 control patients with non-vascular eye diseases: prothrombin times, partial thromboplastin times, plasma fibrinogen, factor V, factor VIII, platelet counts and threshold concentrations of ADP, epinephrine and collagen resulting in secondary platelet aggregation and serotonin release. In contrast, platelet coagulant activities concerned with the early stages of intrinsic coagulation were significantly increased in patients with retinal artery occlusion without hypertension or type IV hyperlipoproteinemia, but generally normal in patients with ischemic optic neuropathy and in patients with retinal artery occlusion associated with hypertension, type IV hyperlipoproteinemia, diabetes mellitus and generalized atherosclerosis. These results are consistent with a platelet contribution to retinal arterial occlusive disease in patients without other known contributing factors such as hypertension, serum lipid abnormalities, diabetes mellitus and generalized atherosclerosis and may have implications regarding prophylaxis.
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PMID:Platelet coagulant activities in arterial occlusive disease of the eye. 50 1

Elevated blood levels of homocysteine are associated with atherosclerosis and thrombotic disease. We previously reported that treatment of cultured endothelial cells with homocysteine increased endogenous factor V activity by activation of the cofactor. Because endothelial cell-associated factor Va would be regulated by the protein C mechanism, the ability of homocysteine-treated arterial and venous endothelial cells to activate protein C was investigated. Both arterial and venous endothelial cells activated protein C; 0.6 mmol/L homocysteine reduced endothelial cell protein C activation by 12%. Maximal inhibition (90%) of protein C activation occurred with 7.5 to 10 mmol/L homocysteine after 6 to 9 hours of incubation. Metabolism of homocysteine was not accelerated by cultured endothelial cells. Investigation of the mechanism(s) by which homocysteine reduced protein C activation indicated that the metabolite did not induce an inhibitor to activated protein C, but in low concentrations acted as a competitive inhibitor to thrombin. These data suggest that perturbation of the vascular endothelial cell protein C mechanism by homocysteine may contribute to the thrombotic tendency seen in patients with elevated blood levels of this metabolite.
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PMID:Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells. 215 69

Embolization of thrombi from ulcerated plaques is an important cause of morbidity from atherosclerotic carotid artery disease. Factors controlling thrombus formation on these lesions are not well understood. Macrophages were isolated from atherosclerotic plaques to assess their potential to promote local fibrin deposition. Plaques were collected from 11 patients undergoing carotid endarterectomy and 9 patients undergoing reconstructive procedures for atherosclerotic disease of their distal aorta or femoral arteries. Blood was also collected concurrently to isolate monocytes. Procoagulant activity (PCA) of carotid macrophages (8.6 +/- 4.1 mU/10(6) cells) was significantly higher than that of macrophages from non-carotid lesions (0.35 +/- 0.20 mU/10(6) cells; P less than 0.05) or blood monocytes from either group of patients. The PCA of carotid plaque macrophages from patients with recent emboli was 16.1 +/- 8.4 mU/10(6) cells (n = 5) compared to 2.4 +/- 0.8 mU/10(6) cells (n = 6) for plaque macrophages from assymptomatic carotid endarterectomy patients. Carotid macrophage PCA was factor V and factor VII dependent. Its functional activity was inhibited by an anti-tissue factor antibody, and immunohistochemical studies on tissue sections from carotid plaques showed tissue factor in areas where macrophages were abundant. These studies demonstrate that macrophages within carotid artery plaques have augmented procoagulant activity compared with blood monocytes and macrophages from other atherosclerotic lesions and indicate that carotid plaque macrophages are activated. Augmented macrophage PCA may contribute to thrombus formation on ulcerated plaques.
Atherosclerosis 1989 Oct
PMID:Procoagulant activity expression by macrophages from atheromatous vascular plaques. 259 31

Platelets contain a vast number of biologically active molecules within cytoplasmic granules which are classified according to their respective distinct ultrastructures, densities and content. The alpha-granule is a unique secretory organelle in that it exhibits further compartmentalization and acquires its protein content via two distinct mechanisms: (1) biosynthesis predominantly at the megakaryocyte (MK) level (with some vestigial platelet synthesis) (e.g. platelet factor 4) and (2) endocytosis and pinocytosis at both the MK and circulating platelet levels (e.g. fibrinogen (Fg) and IgG). The currently known list of alpha-granular proteins continues to enlarge and includes many adhesive proteins (e.g. Fg, von Willebrand factor (vWf) and thrombospodin (TSP)), plasma proteins (e.g. IgG and albumin), cellular mitogens (e.g. platelet derived growth factor and TGF beta), coagulation factors (e.g. factor V) and protease inhibitors (e.g. alpha 2-macroglobulin and alpha 2-antiplasmin). More recently the inner lining of the alpha-granule unit membrane has been demonstrated to contain a number of physiologically important receptors including glycoprotein IIb/IIIa (alpha IIb beta 3) and P-selectin. The alpha-granules originate from small precursor granules which can be observed budding from the trans-Golgi network within the platelet precursor cell the MK. During MK maturation the alpha-granules become very prominent and are ultimately packaged into platelets during thrombopoiesis. The alpha-granular contents are destined for release during platelet activation at sites of vessel wall injury and thus play an important role in haemostasis, inflammation, ultimate wound repair and in the pathogenesis of atherosclerosis.
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PMID:Platelet alpha-granules. 846 33

Thrombosis occurs when there is a breakdown in the balance between thrombogenic factors and protective mechanisms. The thrombogenic factors may be exogenous (e.g. trauma, surgery), endogenous (e.g. cancer, vascular diseases) or both (e.g. atherosclerosis, complicated pregnancy). Defects in the protective mechanisms may be congenital (e.g. factor V R506Q-mutation, deficiency of protein C, protein S or antithrombin) or acquired (e.g. lupus anticoagulans, deficiency of antithrombin in nephrosis). In recent years, research in thromboembolic diseases has been overwhelmed with new observations, rendering it worthwhile to put efforts into the evaluation of thrombotic mechanisms in individuals suffering from or predisposed to thromboembolic diseases. Such efforts will pave the way for more effective prophylaxis in thrombosis-prone patients, more specific treatment of thrombotic diseases, and the mastering of recurrent thrombosis.
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PMID:Thrombogenesis. 868 75

Congenital homocysteinuria is a rare inherited metabolic disorder with early onset atherosclerosis and arterial and venous trombosis. Moderate hyperhomocysteinemia is more frequently encountered and is recognized as an independent cardiovascular risk factor. Several case-control studies demonstrate an association between venous thromboembolism and moderate hyperhomocysteinemia. A patient with moderate hyperhomocysteinemia has a 2-3 relative risk of developing an episode of venous thromboembolism. The occurrence of mild hyperhomocysteinemia in heterozygotes for the mutation of Leiden factor V involves a 10-fold increase in the risk of venous thromboembolism. The biochemical mechanism by which homocysteine may promote thrombosis is not fully recognized. Homocysteine inhibits the expression of thrombomodulin, the thrombin cofactor responsible for protein C activation, and inhibits antithrombin-III binding. Treatment with folic acid reduces the plasma level of homocysteinemia, but no study has demonstrated its efficacy in reducing the incidence of venous thromboembolism or atherosclerosis. Hyperhomocysteinemia should be included in the screening of abnormalities of hemostasis and thrombosis in patients with idiopathic thromboembolism, and mild hyperhomocysteinemia may justify a trial of folic acid.
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PMID:[Homocysteine and venous thromboembolism]. 930 44

Chlamydia pneumoniae infection has been linked to atherosclerosis, but a possible relationship with venous thromboembolism (VTE) has not been sought. We determined circulating anti-C. pneumoniae antibody levels in patients with VTE. We studied 176 case patients with objectively diagnosed VTE and 197 age- and sex-matched healthy controls, in a retrospective study. Acquired risk factors for VTE and frequent predisposing genetic factors (factor V Arg 506 Gln and factor II G 20210 A mutations) were assessed in all the subjects. Anti-C. pneumoniae IgG antibodies were determined by microimmunofluorescence. All positive plasma samples (titer > or =128) were precisely quantified and tested for the presence of specific IgM antibodies. Fifty-four percent of the cases and 15.9% of the controls had specific IgG titers of at least 256 (p <0.0001). The crude odds ratio for VTE was 6.2 (95% CI, 3.8-10.1), and rose to 7.7 (4.5-13.2) after excluding subjects carrying the factor V Arg 506 Gln or factor II G 20210 A mutations. The odds ratio for VTE increased with the IgG titer: the adjusted odds ratios were 2.1 (95% CI, 1.1-4.1), 5.3 (2.7-10.6) and 33.0 (4.4-248.4) for titers of 256, 512 and 1024, respectively. Only one subject (a case patient) with a high IgG titer (> or =256) also had specific IgM. High titers of anti-C. pneumoniae IgG antibodies are frequently found in patients with previous venous thromboembolism. This association deserves to be confirmed in other case-control studies and prospective studies.
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PMID:Demonstration of an association between Chlamydia pneumoniae infection and venous thromboembolic disease. 1089 43

Chlamydia pneumoniae infection has been linked to atherosclerosis, but a possible relationship with venous thromboembolism (VTE) had not been sought. We determined circulating anti-C. pneumoniae antibody levels in patients with VTE. Fifty-four percent of the cases and 15.9% of the controls had specific IgG titers of at least 256 (p<0.0001). The crude odds ratio for VTE was 6.2 (95% CI, 3.8-10.1), and rose to 7.7 (4.5-13.2) after excluding subjects carrying the factor V Arg 506 Gln or factor II G 20210 A mutations. Other studies did not confirm such an association or found a lower odds ratio. This association remains to be confirmed in other case-control or prospective studies.
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PMID:Infection and venous thrombosis. 1367 72

Resistance to activated protein C (APC) has been demonstrated to be a risk factor for venous thromboembolism, but it is not known whether this phenotype is consistent over time. We reinvestigated 2580 subjects from the Vicenza Thrombophilia and Atherosclerosis (VITA) Project to evaluate the prevalence of a consistent APC resistance phenotype in the population. Among the 433 subjects with an APC resistance at first visit, the phenotype was confirmed in all the 74 factor V (FV) Leiden carriers and in 124 of 359 FV Leiden negative subjects (34%). The prevalence of a confirmed phenotype, not associated with FV Leiden, was 4.8% in our population. In a subgroup of subjects previously investigated for heritability of the APC resistance, we confirmed the APC resistance phenotype in seven of 39 (17.9%) subjects with an APC resistant sibling but only in 20 of 408 (4.9%) subjects without a sibling with the same phenotype (P = 0.005). Among the 124 FV Leiden negative subjects with a persistent APC resistance phenotype, 40 (32%) had a plasma factor VIII coagulant activity level above 150 IU/dl and eight (6.4%) were carriers of the G20210A prothrombin allele. APC resistance not due to FV Leiden is a frequent and consistent phenotype in the general population, with a possibly strong genetic influence.
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PMID:Intraindividual consistency of the activated protein C resistance phenotype. 1525 14

A prospective molecular epidemiology study was implemented in a cohort of 98 subjects suffering from severe atherosclerotic lesions requiring removal of an abdominal aorta fragment. We previously published the results relative to detection, in the aorta medium layer, of bulky DNA adducts and fluorescent polycyclic aromatic hydrocarbon-related DNA adducts, oxidative DNA damage, and mitochondrial DNA 4977 common deletion, as well as GSTM1 and GSTT1 gene polymorphisms. We report herein new data, relative to oxidative stress biomarkers, including oxidative DNA damage in both inner and medium aorta layers, malondialdehyde in the medium layer, homocysteine and reduced glutathione in plasma, and those relative to additional gene polymorphisms, including NAT1, NAT2, OGG1, MTHFR, Leiden factor V, and prothrombin. The results of biochemical and molecular analyses were related to survival of the patients, whose average age was 70 at the start of the follow up. During the following 14 years, 71.4% of them died. The results obtained provide evidence for the crucial impact of oxidative stress and certain gene polymorphisms on clinical and biochemical patterns as well as on survival of patients. Survival was significantly affected not only by traditional risk factors for atherosclerosis but also by molecular end-points and adverse gene polymorphisms, and by their combinations.
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PMID:Survival of atherosclerotic patients as related to oxidative stress and gene polymorphisms. 1738 90


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