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)

Serum lipids, lipoprotein (a), plasminogen activator inhibitor and tissue plasminogen activator levels were measured in 260 subjects, constituting a cross-section sample of 30-60-year-old men and women. For Lp(a), there were positive correlations with age and cholesterol, but not with any of other measured parameters. Triglyceride, cholesterol, and HDL-cholesterol (inversely) levels were associated with waist-to-hip girth circumference ratio: this variable remained significant in a multiple regression model. PAI-1 activity and tPA antigen levels were positively associated with triglycerides and inversely associated with HDL-cholesterol. Moreover, tPA antigen was positively related to total cholesterol level. In multiple regression analysis, however, only triglycerides were found to contribute significantly to the variance of tPA antigen and PAI-1 activity levels, when BMI (in men) and abdominal skinfold thickness (in women) were entered into the model. Insulin or glucose postload responses to an OGTT were not independently related to any lipid or fibrinolytic variable. These data demonstrate the importance of anthropometric variables both for fibrinolytic variables and traditional lipid risk factors. Only Lp(a) was found to be largely unrelated to the endocrine-metabolic and anthropometric variables.
Atherosclerosis 1989 Nov
PMID:Interrelationships between plasma levels of plasminogen activator inhibitor, tissue plasminogen activator, lipoprotein (a), and established cardiovascular risk factors in a north Swedish population. 253 10

The release of tissue plasminogen activator (tPA) by vascular endothelial cells during exercise was studied in forty men with insulin-dependent diabetes. Three groups, matched for age and diabetes duration, were defined as: group I (n = 19), normal urinary albumin excretion (less than 30 mg/24 h); group II (n = 11), incipient diabetic nephropathy (30-300 mg albumin excreted per 24 h); and group III (n = 10), clinical diabetic nephropathy (more than 300 mg albumin excreted per 24 h). Nine non-diabetic men served as controls. The rise in tPA antigen with exercise was similar in the controls and group I but significantly smaller in groups II and III (p less than 0.01). The albumin transcapillary escape rate was significantly higher in groups II and III than in group I and normal controls (p less than 0.01). The basal plasma level of von Willebrand factor was higher in groups III (p less than 0.01) and II (difference not significant, p = 0.06) than in group I and normal controls. These findings suggest that insulin-dependent diabetic patients with only slightly raised urinary albumin excretion have general endothelial cell dysfunction or damage. It is not yet clear whether these changes are important in the pathogenesis of thrombosis and atherosclerosis in these patients.
 ...
PMID:Features of endothelial dysfunction in early diabetic nephropathy. 256 40

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.
 ...
PMID:[Monocyte-endothelium relations]. 265 10

Angina presents itself to us as a continuous spectrum of ischemic syndromes. The disease is multifactorial, and within the same patient different pathophysiological mechanisms may occur at different times and in succession. Several factors may be causative at a particular moment of the disease process and the very next moment a different mechanism may prevail or spontaneous improvement may occur. Among these are stable atheroma with episodic increased vasomotor tone, fissured plaques with intraluminal and/or intraintimal thrombus, thrombocyte aggregation in greater than 70% intraluminal narrowing from ulcerated plaques, as well as frank spasm of vessels without major atherosclerosis. Consequently, there will never be one therapy for every case of (un)stable angina nor will there ever be a best therapy for all. Rather, a stepped approach appears the most likely to be successful. This begins with bed rest and requires vasodilator therapy with nitrates and/or Ca2+ antagonists and beta blockade. If this triple therapy does not "cool" the symptoms within 6-12 hours, semiurgent arteriography is indicated. Depending on the pathophysiology found, thrombolytic therapy with streptokinase or tissue plasminogen activator, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) must be carried out early. Heparin in the short term and aspirin in the long term protect best against late complications. The moment is now here when infarction or death after an attack of angina pectoris should be rare.
 ...
PMID:Calcium antagonists for angina pectoris. 289 19

Lp(a) represents a genetically transmitted class of plasma LDL having apo B-100 linked by a disulfide bridge to a glycoprotein, apo(a). Lp(a) is heterogeneous in size and density. Apo(a) is also heterogeneous in size (molecular weight between approximately 300,000 and 700,000) due probably to the polymorphism of both polypeptide and carbohydrate chains. Recent studies have shown that apo(a) has a striking amino acid sequence homology with plasminogen, a serine protease zymogen that following activation to plasmin enters the fibrinolytic system. Apo(a) is severalfold larger than plasminogen (molecular weight approximately 90,000) and also differs from it because it fails to be activated to plasmin. This is due to the fact that arginine is replaced by serine at the site of cleavage by streptokinase, urokinase, or tissue plasminogen activator. A single gene locus appears to control the Lp(a) polymorphism as well as the concentration of the Lp(a) phenotypes in the plasma. Patients with high plasma levels of Lp(a) have been shown to have an increased incidence of cardiovascular disease but a causal relationship has not been firmly established. The information that is being rapidly acquired on the structure of Lp(a) should facilitate the understanding of the molecular basis of the polymorphism of this genetic variant and of the role that the various Lp(a) phenotypes play in atherosclerosis and thrombosis. The potential physiologic role of Lp(a) remains open to inquiry.
 ...
PMID:Lipoprotein(a): a genetically determined lipoprotein containing a glycoprotein of the plasminogen family. 297 66

The metabolism in vitro of exogenous and endogenous arachidonic acid was studied in circulating blood monocytes obtained from control (control group) and cholesterol (0.5%)-fed (cholesterol group) rabbits. The production of superoxide anion (O2-), tissue plasminogen activator (t-PA) and adherence of monocytes were assessed in both groups of animals. The amounts of cyclooxygenase and lipoxygenase products derived from exogenously added [1-14C]AA were not significantly different in monocytes collected from both groups of animals. However, the amounts of PGD2, TXB2 and PGE2 formed from endogenous substrate were decreased significantly in monocytes obtained from the cholesterol group compared to those from the control group. The production of immunoreactive LTB4 was not suppressed significantly in monocytes collected from the cholesterol group. The production of O2- and t-PA was suppressed significantly in monocytes obtained from the cholesterol group and these cells adhered onto glass surfaces more efficiently than control cells. Since the formation of prostanoids from endogenous but not exogenous substrate is reduced, an effect of cholesterol on the liberation of AA from phospholipid pools is implicated.
Atherosclerosis 1986 Aug
PMID:Influence of cholesterol feeding on the production of eicosanoids, tissue plasminogen activator and superoxide anion (O2-) by rabbit blood monocytes. 301 60

Impaired fibrinolysis is believed to promote atherosclerosis and contribute to myocardial infarction. The major triggering factor for fibrinolysis is vascular tissue plasminogen activator (t-PA), and the aim of this study was to evaluate the capacity of human arterial smooth muscle cells (SMC) for induction of fibrinolysis. SMC were plated on labeled fibrin gels, and lysis was measured as release of label. Fibrinolytic capacity was dependent on the phenotypic state of SMC. The "multilayered phenotype" to which SMC modulate after cellular injury had a much lower fibrinolysis-inducing capacity than the more ordinary "monolayered" SMC type. Fibrinolysis was mediated by activation of plasminogen. In long-term experiments under conditions imitating thrombolysis, platelet-derived growth factor promoted fibrinolysis indirectly by increase of SMC number, and a direct effect on cellular production of t-PA was not detected. SMC from atherosclerotic intima had a much lower capacity for induction of fibrinolysis than cells from adjacent nonatherosclerotic intima. SMC also displayed several structurally detectable interactions with the fibrin substratum, such as organization of the gel by means of extension of numerous filamentous processes and contraction and wrinkling of the gel. In conclusion, human arterial SMC in vitro induce fibrinolysis by activation of plasminogen. This capacity is dependent on phenotype and lowered for SMC from atherosclerotic intima, suggesting impairment after arterial injury and in atherosclerosis.
 ...
PMID:Impaired fibrinolysis-inducing capacity for postinjury phenotype of cultivated human arterial and human atherosclerotic intimal smooth muscle cells. 335 71

Apolipoprotein(a) [apo(a)] is a glycoprotein with Mr approximately equal to 280,000 that is disulfide linked to apolipoprotein B in lipoprotein(a) particles. Elevated plasma levels of lipoprotein(a) are correlated with atherosclerosis. Partial amino acid sequence of apo(a) shows that it has striking homology to plasminogen. Plasminogen is a plasma serine protease zymogen that consists of five homologous and tandemly repeated domains called kringles and a trypsin-like protease domain. The amino-terminal sequence obtained for apo(a) is homologous to the beginning of kringle 4 but not the amino terminus of plasminogen. Apo(a) was subjected to limited proteolysis by trypsin or V8 protease, and fragments generated were isolated and sequenced. Sequences obtained from several of these fragments are highly (77-100%) homologous to plasminogen residues 391-421, which reside within kringle 4. Analysis of these internal apo(a) sequences revealed that apo(a) may contain at least two kringle 4-like domains. A sequence obtained from another tryptic fragment also shows homology to the end of kringle 4 and the beginning of kringle 5. Sequence data obtained from two tryptic fragments show homology with the protease domain of plasminogen. One of these sequences is homologous to the sequences surrounding the activation site of plasminogen. Plasminogen is activated by the cleavage of a specific arginine residue by urokinase and tissue plasminogen activator; however, the corresponding site in apo(a) is a serine that would not be cleaved by tissue plasminogen activator or urokinase. Using a plasmin-specific assay, no proteolytic activity could be demonstrated for lipoprotein(a) particles. These results suggest that apo(a) contains kringle-like domains and an inactive protease domain.
 ...
PMID:Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. 347 6

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

Human tissue plasminogen activator holds promise for the dissolution of coronary thrombi by intravenous administration and without systemic anticoagulation. Prior animal experiments have been conducted only in vessels without disease. To test the thrombolytic efficacy of recombinant tissue plasminogen activator in the presence of diseased intima, an established model of atherosclerosis was utilized. The aorta of 16 New Zealand white rabbits (2 to 3 kg) was made atherosclerotic by balloon endothelial denudation and concurrent 1% cholesterol feeding for 8 weeks. An aged (24 hour) heterologous (human) clot, labeled with I-125 fibrinogen was injected into the distal aorta and produced thrombotic occlusion. After 1 hour of thrombosis (control period), recombinant tissue plasminogen activator (100,000 IU approximately equal to 1 mg protein, n = 6) or streptokinase (100,000 IU, n = 5) or saline solution (n = 5) was systemically infused over 30 minutes. Serial blood samples, obtained to determine fractional change in blood radioactivity over time, showed a fourfold increase of blood radioactivity after tissue plasminogen activator and streptokinase infusion compared with the control period (47,400 +/- 3,300 [mean +/- standard error] versus 11,800 +/- 300 counts/min, p less than 0.001). Time to 50% of maximal thrombolysis was 41 +/- 14 minutes (+/- standard deviation) for tissue plasminogen activator versus 63 +/- 16 minutes for streptokinase (p less than 0.01). In six of six rabbits receiving tissue plasminogen activator and four of five rabbits receiving streptokinase, reestablishment of distal aortic flow was detected via the indwelling catheter within 25 minutes of drug infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Thrombolysis with recombinant tissue plasminogen activator in atherosclerotic thrombotic occlusion. 403 73


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