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)

Urokinase plasminogen activator (uPA) has been implicated in the healing responses of injured arteries, but the importance of its various properties that influence smooth muscle cell (SMC) proliferation and migration in vivo is unclear. We used three recombinant (r-) forms of uPA, which differ markedly in their proteolytic activities and abilities to bind to the uPA receptor (uPAR), to determine, which property most influences the healing responses of balloon catheter injured rat carotid arteries. After injury, uPA and uPAR expression increased markedly throughout the period when medial SMCs were rapidly proliferating and migrating to form the neointima. Perivascular application of uPA neutralizing antibodies immediately after injury attenuated the healing response, significantly reducing neointima size and neointimal SMC numbers. Perivascular application of r-uPAwt (wild type uPA) or r-uPA/GDF (r-uPA with multiple mutations in its growth factor-like domain) doubled the size of the neointima. Four days after injury these two uPAs nearly doubled neointimal and medial SMC numbers in the vessels, and induced greater reductions in lumen size than injury alone. Proteolytically inactive r-uPA/H/Q (containing glutamine rather than histidine-204 in its catalytic site) did not affect neointima or lumen size. Also, in contrast to the actions of proteolytically active uPAs, tissue plasminogen activator (tPA) did not affect the rate of neointima development. We conclude that uPA is an important factor regulating the healing responses of balloon catheter injured arteries, and its proteolytic property, which cannot be mimicked by tPA, greatly influences SMC proliferation and early neointima formation.
Atherosclerosis 2001 Dec
PMID:Urokinase plasminogen activator augments cell proliferation and neointima formation in injured arteries via proteolytic mechanisms. 1173 Aug 9

Fibrinolytic activity has been reported to be decreased in atherosclerosis. Recently, annexin II was identified as a coreceptor on endothelial cells for plasminogen and tissue plasminogen activator. In this study, we examined whether recombinant annexin II (rAN II) protein can modulate fibrinolytic activity on vascular endothelium in vitro and in vivo. The effect of rAN II on human umbilical vein endothelial cells (HUVECs) was measured. Addition of a fluorescent plasmin substrate revealed that HUVECs treated with rAN II exhibited significantly more plasmin generation than those treated with BSA. Moreover, rAN II treatment of HUVECs restored plasmin generation impaired by plasminogen activator inhibitor-1 or homocysteine pretreatment. In a rat carotid artery thrombus model, the patency of thrombosed carotid arteries was significantly enhanced by rAN II injection, in contrast to BSA injection, without systemic blood coagulation dysregulation. We found that rAN II enhanced plasmin generation on vascular endothelium in vitro and reduced thrombus formation in vivo, and concluded that enhancement of endothelial fibrinolytic activity by annexin II could modulate the hypercoagulable state of atherosclerosis. Further study of rAN II in vitro and in vivo may lead to the establishment of novel therapeutic approaches to thrombogenic vascular disease.
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PMID:Recombinant annexin II modulates impaired fibrinolytic activity in vitro and in rat carotid artery. 1173 91

We sought to assess the longitudinal stability of risk factors for atherosclerosis and thrombosis. including several coagulation. fibrinolysis, and inflammation factors, in frozen plasma samples stored at -70 degrees C for months or years. We reviewed data collected on 29 different control pools over periods ranging from 7 to 59 months for two functional assays (factor VII and fibrinogen) and seven antigen measurements (C-reactive protein. D-dimer, plasmin-alpha2-antiplasmin complex, plasminogen activator inhibitor-1, protein C, protein S, and tissue plasminogen activator), totaling more than 15,000 data points. Screening of the data using least squares regression revealed only sporadic associations between monthly means and time, with no consistent trends. Analysis by repeated measures and summary measure methods revealed no evidence of sample degradation over time for the factors studied. Our finding of longitudinal stability in the biochemical properties of frozen plasma strengthens the presumption of sample stability on which molecular epidemiologic studies are based.
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PMID:Longitudinal stability of coagulation, fibrinolysis, and inflammation factors in stored plasma samples. 1177 19

Hyperinsulinemia and hyperglycemia have been associated with vascular injury such as atherosclerosis in diabetes mellitus. Recently, annexin II, a member of annexin family proteins, has been found to work as co-receptor on endothelial cells for plasminogen and tissue plasminogen activator, facilitating plasmin generation on the surface of vascular endothelium. In this review, we overviewed the effect of glucose and insulin on plasmin generation in endothelial cells and its potential modulation by recombinant annexin II (rAN II) based on our data.
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PMID:Potential role of recombinant annexin II in diabetic vascular injury. 1179 80

Acute myocardial infarction is caused by thrombotic occlusion of a coronary artery at the site of a ruptured or eroded atheromatous plaque. The maintenance and regulation of tissue perfusion critically depend upon the integrity of endothelial function and the release of potent endothelium-derived factors, such as the fibrinolytic factor tissue plasminogen activator (tPA). Atherosclerosis and cigarette smoking are associated with dysfunction of the endothelium, and in particular, appear to impair the acute local endogenous fibrinolytic activity. This provides a potential mechanism whereby atherosclerosis and cigarette smoking can markedly influence the initiation, propagation, and resolution of the acute and chronic thrombotic complications of coronary artery disease through reductions in the capacity to release tPA acutely.
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PMID:Atherosclerosis, cigarette smoking, and endogenous fibrinolysis: is there a direct link? 1182 78

von Willebrand factor (vWF), thrombomodulin and tissue plasminogen activator antigen (tPAag) are regarded as markers of endothelial activation and/or damage. Elevated levels have been associated with atherosclerotic disease states. The aim of the present study was to compare the levels of vWF, thrombomodulin and tPAag in patients with coronary heart disease (CHD) and matched healthy individuals to see if they discriminated significantly between the study groups also after adjustment for established CHD risk factors. Patients (n=193) in various stages of CHD and matched controls (n=193) were included. To evaluate possible influence of acute phase reaction, reinvestigation was performed after 6 months. We observed elevated levels of vWF (P<.001) and tPAag (P<.001) but not thrombomodulin (P=.082) in CHD patients when compared to controls, still statistically significant after 6 months and also after adjustment for established risk factors. Our results indicate that vWF and tPAag but not thrombomodulin in the present population are independent markers of atherosclerosis.
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PMID:Increased levels of endothelial haemostatic markers in patients with coronary heart disease. 1186 3

The study was aimed at investigating the effects, after treatment for 1 year, of two different statins on the levels of circulating biochemical markers of endothelial function in patients with established coronary heart disease, with the hypothesis that statins might reduce these levels. Twenty-eight patients were randomized to treatment with atorvastatin and 30 to simvastatin for 1 year. The starting dose in both groups was 20 mg/day. Soluble forms of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined to assess inflammatory activity of the endothelium, and tissue plasminogen activator antigen (tPAag), von Willebrand factor and thrombomodulin for evaluation of the haemostatic function. In the total study population there were significantly reduced levels after 1 year treatment in ICAM-1 (P<0.001), E-selectin (P=0.022) and P-selectin (P<0.001), whereas a significant increase was observed in VCAM-1 (P=0.003). Almost the same pattern was seen within both groups although the increase in VCAM-1 was only seen in the simvastatin group (P=0.017). An overall reduction in tPAag was further observed (P=0.048). The reduction in proinflammatory and to some extent haemostatic markers of endothelial function after 1 year treatment with either simvastatin or atorvastatin may be indicative of a less activated state of the endothelium which possibly may contribute to modulation of the progression of atherosclerosis.
Atherosclerosis 2002 May
PMID:Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease. 1194 12

The aim of this study was to determine differences in atherothrombotic risk factors in South Asian subjects with a history of ischaemic stroke and South Asian subjects free from personal and family history of clinically detectable stroke. Eighty South Asian patients with ischaemic stroke (confirmed on cranial computerised scan) and 80 South Asian controls with similar age and gender distributions were recruited at random. The frequency of hypertension (P=<0.0001), myocardial infarction (P=0.003) and diabetes mellitus (<0.0001) were significantly higher in stroke patients. Stroke patients had lower high-density lipoprotein cholesterol (0.95 vs. 1.1 mmol/l, P=<0.0001), higher plasma glucose (8.1 vs. 6.6 mmol/l, P=0.01) and trendwise higher HBA(1C) (6.4 vs. 6.0%, P=0.09). There was no difference in insulin levels but insulin resistance was significantly higher in stroke patients (3.75 vs. 2.66, P=0.01). Stroke patients showed elevated levels of fibrinogen (3.78 vs. 3.41 mg/dl, P=0.02), von Willebrand factor (1.78 vs. 1.50 IU/ml, P=0.006) and tissue plasminogen activator (12.8 vs. 11.3 ng/ml, P=0.04), but the differences did not persist after adjustment for glucose, triglycerides, HDL, WHR, and BMI. Higher levels of fibrinogen, von Willebrand factor and t-PA in South Asian stroke patients disappeared after adjustment for features of insulin resistance syndrome but persisted after adjustment for presence of diabetes, confirming that these changes are essentially dependant on features of insulin resistance syndrome. A prospective study would be required to elucidate the role of thrombotic risk factors in South Asians with ischaemic stroke.
Atherosclerosis 2002 Aug
PMID:Increased fibrinogen, von Willebrand factor and tissue plasminogen activator levels in insulin resistant South Asian patients with ischaemic stroke. 1205 85

A healthy endothelium plays a central role in cardiovascular control. Therefore, endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between pro-inflammatory and anti-inflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. ED is closely related to different risk factors of atherosclerosis, to their intensity and their duration. The involvement of risk factors in ED is also supported by results of intervention studies that showed regression of ED with treatment of risk factors. The common denominator whereby different risk factors cause ED is most probably increased oxidative stress and/or inflammation. ED promotes atherosclerosis and probably plays an important role in the development of thrombotic complications in the late stages of the disease. As ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been sought. Detection of ED is based on tests of endothelium-dependent vasomotion (dilation capability of peripheral and coronary arteries) and on circulating markers of endothelial function (endothelin-1, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, adhesion molecules). Using these tests it is possible to follow the dose-response of harmful effects or risk factors, and the effects of preventive procedures on vessel wall function.
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PMID:Endothelial dysfunction in the pathogenesis of atherosclerosis. 1211 Jul 69

Patients on continuous ambulatory peritoneal dialysis (CAPD) often have abnormalities of lipid metabolism or coagulation and fibrinolysis, these patients may thus be more susceptible to atherosclerosis than those on hemodialysis. It has been reported that hypercoagulability and hyperfibrinolysis are correlated with abnormalities of lipid metabolism. Therefore, we investigated the effect of a decrease in lipids on the coagulation and fibrinolysis system in CAPD patients with hyperlipidemia who received lipid-lowering therapy. The patients included 5 men and 13 women, with a mean age of 52.5 years. Pravastatin sodium (10 mg/day) and ethyl icosapentate (1800 mg/day) were administered concomitantly for 8 weeks. Lipid levels and coagulation/fibrinolysis parameters were measured before and after therapy. The patients were divided into two groups depending on their response to therapy: responders showed a decrease in total cholesterol or triglycerides by at least 20% and non-responders showed less improvement. In the responders, the levels of protein C, tissue plasminogen activator/plasminogen activator inhibitor-I complex, factor XIII, alpha2-plasmin inhibitor, and D-dimer were significantly lower after therapy than before therapy. Protein C, factor XIII, and alpha2-plasmin inhibitor were also significantly decreased after therapy in non-responders, but the extent of the decrease was smaller. The plasminogen level was significantly increased after therapy in non-responders. These findings suggest that a decrease in lipid levels and/or some other action by lipid-lowering agents may correct abnormalities of coagulation and fibrinolysis in CAPD patients.
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PMID:Lipid-lowering therapy and coagulation/fibrinolysis parameters in patients on peritoneal dialysis. 1211 34


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