Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coagulation factor VIII, von Willebrand factor, antithrombin, fibrinogen, plasminogen activator capacity, and inhibitors of fibrinolysis, including a recently discovered fast inhibitor of tissue plasminogen activator, were measured three to six months after myocardial infarction in 116 male and 32 female patients aged less than 45 and in 136 age and sex matched random controls. Plasma concentrations of fibrinogen and the fast inhibitor of tissue plasminogen activator were raised in male patients (with or without correction for orosomucoid levels, blood group distribution, tobacco and alcohol consumption, and weight/height index) and plasminogen activator capacity was reduced. In female patients the concentrations of factor VIII, von Willebrand factor, the fast inhibitor of tissue plasminogen activator, alpha 2-antiplasmin, and C1 inhibitor were significantly increased. The increase in factor VIII concentrations depended strongly on a persisting inflammatory response. Multivariate analysis indicated that a combination of fibrinogen and tissue plasminogen activator inhibitor concentrations gave the best independent discrimination between male patients and controls. For female patients the best combination was von Willebrand factor and tissue plasminogen activator inhibitor. Male patients with multiple vessel atheromatosis at coronary angiography had higher fibrinogen concentrations than those with atheromatosis of a single vessel. Atheromatosis was defined as sharp-edged, plaque-like, or irregular indentations, often multiple, into the vessel lumen without features suggesting fibromuscular hyperplasia.
 ...
PMID:Haemostatic function in myocardial infarction. 394 83

The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.
 ...
PMID:Release of plasminogen activator from isolated perfused dog heart. 403 71

Using a semi-quantitative, histochemical fibrin slide technique, plasminogen activator (PA) activity was determined in 65 atherosclerotic arteries obtained from 65 patients during surgery -42 during resection of the infrarenal part of the aorta, and 23 from a leg artery in patients undergoing a below-knee amputation. In 12 of the patients undergoing resection of the aorta, another specimen was obtained from a collateral artery free from atherosclerotic lesions. PA activity in the atherosclerotic aortic specimens was significantly decreased compared with that in collateral arteries, and low PA activity was also found in leg arteries.
Atherosclerosis 1984 Jan
PMID:Decreased fibrinolytic activity in human atherosclerotic vessels. 653 86

Fibrin contains a factor which promotes growth of the mesenchymal cells and such may be related tissue repair. Effects of fibrin and fibrinogen degradation products (FDP) on the growth of smooth muscle cells (SMC) of rabbit aortas in culture were investigated, in relation to atherogenesis. Fibrin, free from plasminogen enhanced the proliferation of SMC during the experimental period of 48 h. Fibrin, rich in plasminogen also stimulated the proliferation of SMC within 24 h, but inhibited it after 48 h. FDP (fragments D and E) inhibited the proliferation of SMC. SMC of rabbit aortas demonstrated plasminogen activator activity. Thrombin and urokinase exhibited no promoting effects on the growth of SMC. These results support the hypothesis that the proliferation of SMC is stimulated by fibrin and later inhibited by FDP, as produced by the fibrinolytic activity of SMC. It is proposed that the metabolism of fibrin in the arterial wall may be of importance in the regulation of SMC proliferation and that the coagulation-fibrinolysis system may play a significant role in atherogenesis.
Atherosclerosis 1982 Aug
PMID:Effects of fibrin and fibrinogen-degradation products on the growth of rabbit aortic smooth muscle cells in culture. 713 18

Branching regions of the aorta are predilection regions for atherosclerosis. The intima in the branching regions of the normal aorta shows a constantly increased plasminogen activator activity from early life. At these areas, the endothelium is also damaged, it shows increased permeability, etc. The constantly increased plasminogen activator activity (local plasmin production) might play a protective role or on the might participate in the initiation of atherosclerosis at the branching regions through a number of proved or suggested mechanisms. No matter what the actual role of the locally increased plasminogen activator activity in the initiation of atherosclerosis is, the role of the fibrinolytic system in the progression of the atherosclerotic lesion seems to be clear. There is an accumulation of evidence that the impaired fibrinolytic activity in atherosclerotics participates in the progression and the complications of the disease.
 ...
PMID:A new hypothesis: possible mechanisms in the involvement of the increased plasminogen activator activity in branching regions of the aorta in the initiation of atherosclerosis. 719 89

Among endothelial secretogogues prostacyclin (PGI2), nitric oxide (NO) and tissue plasminogen activator (t-PA) play a crucial role in maintaining thromboresistance, tone and structure of the vascular wall. Most receptor agonists, such as B2 kinin receptor agonists, or shear force produce a coupled release of all three secretogogues, and therefore interactions between them are to be expected. Essentially, PGI2 is a platelet suppressant, NO a vasodilator and t-PA a fibrinolytic agent. These and other properties of endothelial secretogogues supplement each other in protecting the cardiovascular system from injuries. It is not surprising that disturbances of the secretory function of endothelial cells are associated with atherosclerosis, diabetes, thrombosis or hypertension. Traditionally, PGI2, NO, t-PA or their substitutes are used individually for the treatment of peripheral arterial disease, angina pectoris or acute myocardial infarction. In light of recent findings, their joint administration can be advocated. For instance, NO donors will potentiate platelet-suppressant action of PGI2 analogues, whereas exogenous PGI2 or TXA2 synthase inhibitors (i.e. following increase in endogenous PGI2) will abolish a paradox of prothrombotic action of t-PA or streptokinase. The replacement therapy with PGI2, NO or t-PA should match as closely as possible the physiologically coupled release of these secretogogues.
 ...
PMID:Interactions between endothelial secretogogues. 754 32

Studies with transgenic mice over- or under-expressing components of the fibrinolytic system, have revealed a significant role of this system in fibrin clot surveillance, reproduction, (vascular) wound healing, brain function, health and survival. The distinct phenotypes associated with single loss and the more severe phenotype associated with combined loss of plasminogen activator gene function suggest that through evolution, both plasminogen activators have evolved with specific but overlapping biological properties. Interestingly, the role of the fibrinolytic system in thrombosis and vascular wound healing became more apparent after challenging mice single deficiencies of plasminogen activators with an inflammatory, or traumatic challenge, respectively. It therefore seems warranted to examine possible consequences of loss of plasminogen activator gene function in other processes including atherosclerosis, neoangiogenesis, inflammatory lung and kidney disease and malignancy. The plasminogen activator knock-out mice with their thrombotic phenotypes are also valuable models to evaluate whether adenoviral mediated gene-transfer of wild-type or mutant plasminogen activator genes is able to restore normal thrombolytic function and to prevent thrombosis. Preliminary evidence suggests that impaired thrombolysis of t-PA deficient mice can be completely restored using adenoviral-mediated gene transfer of rt-PA (Carmeliet et al, 1994c). In addition, analysis of neointima formation in plasminogen activator deficient mice suggests that controlled reduction of fibrinolytic activity in the vessel wall might be beneficial for the prevention or reduction of restenosis. Whether this can be achieved with gene transfer methodologies remains to be defined.
 ...
PMID:Physiological consequences of over- or under-expression of fibrinolytic system components in transgenic mice. 754 69

We investigated the relationship between fasting insulin level and various hemostatic factors, including fibrinolytic factors (active plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (tPA)-PAI-1 complex, plasmin-alpha 2-plasmin inhibitor (PIC), and D-dimer), coagulation factors (activated factor VII, factor VII coagulant activity and antigen, factor VIII, factor X, and fibrinogen), coagulation inhibitors (antithrombin III, heparin cofactor II, and protein C), and an acute phase marker (sialic acid) in 102 healthy individuals aged > or = 75 years (46 men and 56 women). Active PAI-1 levels had a significant negative correlation with PIC levels (r = -0.342, P = 0.0006), indicating that PAI-1 influences in vivo fibrinolytic activity in the very elderly. Gender differences were found in the relationship between insulin and hemostatic abnormalities, with the insulin level being positively correlated with coagulation factors in men (factor VIII activity: r = 0.422, P < 0.01; factor VII activity: r = 0.386, P < 0.01) and with hypofibrinolysis in women (active PAI-1: r = 0.549, P < 0.0001). Insulin levels were positively correlated with the levels of factor VII antigen and factor VII activity in men (P < 0.01), but there was no correlation with activated factor VII levels. The fasting insulin level was also correlated with the levels of heparin cofactor II and sialic acid in men (P < 0.05). However, other hemostatic factors were not related to the insulin level in either sex.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1995 Aug
PMID:Gender differences of disturbed hemostasis related to fasting insulin level in healthy very elderly Japanese aged > or = 75 years. 757 76

The plasminogen/plasmin or fibrinolytic system with its physiological triggers, tissue-type plasminogen activator, and urokinase-type plasminogen activator has been presumed to participate in normal and pathological processes of the vessel wall such as blood clot dissolution (thrombolysis), hemostasis, aneurysm formation, neovascularization, restenosis, and atherosclerosis. The implied role of the fibrinolytic system in vivo is, however, deduced from correlations between fibrinolytic activity and (patho)physiological phenomena, which does not allow establishing a cause/consequence relationship. Gene targeting and gene transfer technologies allow establishment of the in vivo role of gene products more conclusively. This article reviews briefly the findings of such studies on thrombolysis/thrombosis, hemostasis, neointima formation, atherosclerosis, and associated effects on survival.
 ...
PMID:Gene targeting and gene transfer studies of the plasminogen/plasmin system: implications in thrombosis, hemostasis, neointima formation, and atherosclerosis. 761 62

Type 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor plasminogen activator and has been found to be increased in a number of clinical conditions generally defined as prothrombotic. Since in aging and in atherosclerosis the changes observed in the endothelium resemble those of in vitro aged endothelial cells, we have examined the expression of PAI-1 in cells at different population doublings. In senescent endothelial cells, PAI-1 mRNA and protein are constitutively high, but uninducible by exogenous interleukin 1 alpha as well as by the phorbol ester TPA. Interestingly the increase of PAI-1 levels correlates with the upregulation of interleukin 1 alpha, which characterizes endothelial cell senescence. Since PAI-1 expression is not increased in young cells made nondividing by contact inhibition, we anticipate that PAI-1 expression can be used as an appropriate marker of endothelial senescence. Moreover, PAI-1 was not upregulated in senescent or in progeric human fibroblasts, which do not overexpress interleukin 1 alpha, thus suggesting that multiple pathways may exist to regulate aging of human fibroblasts and endothelial cells.
 ...
PMID:Senescence-dependent regulation of type 1 plasminogen activator inhibitor in human vascular endothelial cells. 762 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>