Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain arachidonic metabolites may play a pathogenic role in psoriasis. Platelets are rich sources of 12-hydroxy-eicosatetraenoic acid (12-HETE) and thromboxane A2, mediators of skin inflammation and platelet aggregation, respectively. We have studied untreated psoriatic patients without a history of diabetes mellitus and smoking. In psoriatics, platelet aggregation elicited by thrombin, ADP, and ristocetin was significantly enhanced as compared with healthy adult volunteers. Enhancement of platelet aggregation was detected in patients with both minimal and widespread disease. The formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), a cyclooxygenase product, and 12-HETE, a 12-lipoxygenase product, was increased in psoriatics with widespread disease but not in those with minimal disease. Formation of 12-HETE was stimulated to a higher degree (125%) than HHT (98%) in psoriasis (P less than 0.05). Addition of platelet-derived 12-HETE to cultured human epidermal keratinocytes resulted in a stimulation of the DNA synthesis (68% at 10(-7) M). These data suggest that platelet activation occurs in psoriasis, and that release of inflammatory and mitogenic compounds by activated platelets may play a role in the pathophysiology of psoriasis. Whether enhanced platelet aggregation in psoriasis is associated with occlusive vascular disease needs further investigation.
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PMID:Increased aggregation and arachidonic acid transformation by psoriatic platelets: evidence that platelet-derived 12-hydroxy-eicosatetraenoic acid increases keratinocyte DNA synthesis in vitro. 243 57

Since intravascular and endoparietal fibrin deposition is thought to be involved in the development of atherosclerosis, we measured factor XIII activity and its subunit 'a' and 'b' concentrations against a background of other haemostasis parameters in diabetics with angiopathy and in 2 control groups (healthy subjects and diabetics without vascular complications). Diabetics with angiopathy revealed a significant increase of factor XIII activity as well as its subunit concentrations. They also had significantly elevated anti-thrombin III, alpha 2 macroglobulin, alpha 1 antitrypsin, C1 inhibitor, fibrinogen, FDP concentrations and prolongation of euglobulin lysis time. The highest factor XIII levels were found in diabetics with renal failure. We suppose that increased factor XIII level and other observed changes of haemostasis in patients with diabetic angiopathy might promote intravascular and endoparietal fibrin deposition and contribute to the development of atherosclerotic complications of diabetes.
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PMID:Plasma factor XIII and some other haemostasis parameters in patients with diabetic angiopathy. 243 83

In an earlier study on post-operative thromboembolism in neurosurgery the incidence of deep vein thromboses (DVT) diagnosed by the fibrinogen uptake test and phlebography was reduced to the same extent by two different prophylactic methods (low dose heparin or calf muscle stimulation + dextran). However, patients with lower limb paresis due to a brain lesion experienced relatively often a less successful prophylaxis compared to patients with spinal lesions. There are few reports on successful clinical methods for haematological screening of post-operative DVT. The aim of this study was to examine possible haematological indicators for post-operative thromboembolism and secondarily to elucidate whether there exist some special coagulatory or fibrinolytic characteristics in patients who had been operated upon for brain lesions. We have studied two specific coagulatory factors (FPA reflecting thrombin generation and B beta 15-42 reflecting plasmin activity) in connection with neurosurgical operations. Patients in the above-mentioned study on post-operative DVT operated upon for malignant cerebral tumours or intracranial vascular disease exhibited post-operatively higher values for FPA compared to other neurosurgical diagnoses. B beta 15-42 was higher in the malignant tumour group and almost significantly higher in the intracranial vascular group (p less than 0.065). These differences could not be ascribed to the occurrence of DVT. Another 15 patients divided into a minor and a major lesion group were investigated with determination of both parameters pre- and post-operatively. Concerning FPA an increase was noticed post-operatively compared to pre-operatively in the major lesion group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrinopeptide A and fibrinogen fragment B beta 15-42 and their relation to the operative trauma and post-operative thromboembolism in neurosurgical patients. 244 55

Focal adhesion of leukocytes to the blood vessel lining is a key step in inflammation and certain vascular disease processes. Endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell surface glycoprotein expressed by cytokine-activated endothelium, mediates the adhesion of blood neutrophils. A full-length complementary DNA (cDNA) for ELAM-1 has now been isolated by transient expression in COS cells. Cells transfected with the ELAM-1 clone express a surface structure recognized by two ELAM-1 specific monoclonal antibodies (H4/18 and H18/7) and support the adhesion of isolated human neutrophils and the promyelocytic cell line HL-60. Expression of ELAM-1 transcripts in cultured human endothelial cells is induced by cytokines, reaching a maximum at 2 to 4 hours and decaying by 24 hours; cell surface expression of ELAM-1 protein parallels that of the mRNA. The primary sequence of ELAM-1 predicts an amino-terminal lectin-like domain, an EGF domain, and six tandem repetitive motifs (about 60 amino acids each) related to those found in complement regulatory proteins. A similar domain structure is also found in the MEL-14 lymphocyte cell surface homing receptor, and in granule-membrane protein 140, a membrane glycoprotein of platelet and endothelial secretory granules that can be rapidly mobilized (less than 5 minutes) to the cell surface by thrombin and other stimuli. Thus, ELAM-1 may be a member of a nascent gene family of cell surface molecules involved in the regulation of inflammatory and immunological events at the interface of vessel wall and blood.
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PMID:Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. 246 35

Diabetes mellitus (DM) is associated with an increased incidence of vascular complications. Abnormalities in the hemostatic system contribute at least in part to the development of vascular disease or atherosclerosis. In order to assess the actual degree of activation of the coagulation and fibrinolytic systems in diabetics, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP) were measured together with tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 18 patients with DM (three patients with type I DM and 15 with type II DM). Mean plasma levels of TAT (2.5 +/- SD 1.2 ng/mL) and PAP (0.9 +/- 1.2 micrograms/mL) were significantly elevated in diabetics as compared with healthy subjects (1.7 +/- 0.3 ng TAT and 0.2 +/- 0.1 micrograms PAP per mL of plasma; p = 0.009 and 0.02, respectively). Plasma antigen concentration of t-PA but not of PAI-1 was also elevated. No difference was found in the levels of these variables between type I and type II diabetics or between patients with and without retinopathy or nephropathy. These findings indicate that continuous activation of coagulation and fibrinolysis actually occurs in the majority of the patients with DM.
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PMID:Activation of blood coagulation and fibrinolysis in diabetes mellitus: evaluation by plasma levels of thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex. 238 33

Individuals with diabetes mellitus may have increased in vivo platelet activity. Abnormal platelet function could contribute to the increased incidence of vascular disease in diabetes mellitus. The biochemical mechanism(s) for platelet hyperactivation is unknown. We examined the hypothesis that platelet phosphoinositide turnover, a key signal-transducing mechanism involved in platelet activation, was abnormal in diabetic subjects. Platelets were harvested from 16 subjects with insulin-dependent diabetes mellitus (IDDM) and 19 healthy, nondiabetic control subjects of comparable age. Plasma beta-thromboglobulin (beta-TBG), a specific marker of platelet activity in vivo, was increased in IDDM (67.1 +/- 7.3 ng/ml) compared with control (41.0 +/- 6.0 ng/ml) subjects (P less than .005). [32P]orthophosphate (32Pi) incorporation into the individual phosphoinositides and phosphatidic acid (PA) reached isotopic equilibrium by 120 min for IDDM and control subjects. Specific activity (dpm 32P/micrograms phosphorus) of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was not different between IDDM and control subjects. Under these conditions, basal 32Pi incorporation into PIP2 and PIP but not phosphatidylinositol (PI) or PA was significantly lower in IDDM subjects. There was significantly decreased [32P]PIP2 and [32P]PIP hydrolysis and decreased [32P]PA formation in IDDM after platelet stimulation with 4 U/ml human thrombin. There were no differences in [32P]PI hydrolysis between the two groups. The mass of PIP2 was reduced (P less than .005) in the platelets from IDDM (0.71 +/- 0.23 nmol/10(9) platelets) compared with control (1.65 +/- 0.53 nmol/10(9) platelets) subjects. Similarly, PIP was lower (P less than .001) in IDDM (0.66 +/- 0.09 nmol/10(9) platelets) than in control (2.92 +/- 0.43 nmol/10(9) platelets) subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased platelet phosphoinositide turnover and enhanced platelet activation in IDDM. 254 8

Heparin-induced thrombosis is due to an immune-mediated activation of circulating platelets and has significant clinical implications for patients with vascular disease. The purpose of this article was (1) to define the biochemical mechanisms of heparin-induced platelet activation (HIPA) and (2) to determine the relationship between thromboxane A2 (TxA2) synthesis and platelet granule release. In two patients with confirmed HIPA, heparin (3 U/ml) induced extensive platelet aggregation (61.5%), release of 14C-serotonin (81.5% of releasable 14C-serotonin, a dense granule marker) and platelet factor 4 (63.7% of releasable platelet factor 4, an alpha granule marker) and generation of TxB2, a stable metabolite of TxA2 (100% relative to serum control). In one patient heparin did not induce release of n-acetyl-beta-glucosaminadase (N-AC, a lysosomal granule marker), and aspirin (4 mmol/L), which abolished TxA2 synthesis, prevented aggregation and granule release. In the second patient heparin did induce release of N-AC (39.7% of releasable N-AC) and aspirin, despite abolishing TxA2 synthesis, did not prevent aggregation or granule release. In contrast, by elevating intracellular cyclic adenosine monophosphate, iloprost (0.01 mumol/L), a stable prostacyclin analogue, prevented heparin-induced aggregation, granule release, and TxB2 generation in both patients. Thus we show (1) HIPA can proceed independently of TxA2 synthesis; (2) heparin in certain patients can release lysosomal hydrolases, thus mimicking strong platelet agonists such as thrombin; and (3) iloprost but not aspirin prevents HIPA regardless of the biochemical pathways involved.
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PMID:Heparin-induced platelet activation: the role of thromboxane A2 synthesis and the extent of platelet granule release in two patients. 270 25

Because diabetic vascular disease is accompanied by a state of hypercoagulability, manifested by increased thrombin activity and foci of intravascular coagulation, we investigated whether a specific procoagulant property of the endothelium--production and surface expression of tissue factor--is modified by elevated glucose concentrations. In unperturbed human vascular endothelial cells, tissue factor mRNA and expression of the functional protein were undetectable and were not induced by 10-12 days of exposure to 30 mM glucose. In thrombin-stimulated cultures, tissue-factor expression was related inversely to cellular density, with confluent cultures producing (per 10(5) cells) half the amount of tissue factor measured in sparse cultures. Cells exposed to high glucose and studied when cell number and thymidine incorporation were identical to control cells manifested increased tissue-factor mRNA level and functional protein production in response to thrombin (P = .002). This effect was not attributable to hypertonicity and was not observed after short exposure to high glucose. In contrast, the tissue-factor response to interleukin 1, a modulator of endothelial function in the context of host defense, was decreased in cells cultured in high glucose (P = .04). These findings indicate that exposure to high glucose can alter tissue-factor gene expression in perturbed vascular endothelium. The reciprocal effects of high glucose on the tissue-factor response to thrombin and interleukin 1 points to different pathways of tissue-factor stimulation by the two agents and suggests functional consequences pertinent to the increased thrombin activity and compromised host-defense mechanisms observed in diabetes.
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PMID:Modification of tissue-factor mRNA and protein response to thrombin and interleukin 1 by high glucose in cultured human endothelial cells. 278 75

Effects of co-dergocrine mesylate (Hydergine), a drug widely used for the therapy of cerebral vascular disease on local platelet accumulation in the carotid artery region was studied by means of the platelet uptake ratio (PUR) and on the systemic platelet-vascular wall interaction as calculated from platelet half-life were investigated. A placebo controlled, double blind, randomised protocol was used, 18 patients were treated with co-dergocrine and compared to placebo (n = 18). Co-dergocrine treatment resulted in a significant decrease in platelet deposition, PUR decreased from 1.28 +/- 0.05 before treatment to 1.25 +/- 0.06 on day 5 of therapy with a statistically significant (p less than 0.001) in the paired comparison. In the control group the corresponding changes from 1.29 +/- 0.04 before to 1.28 +/- 0.04 did not show a p-value of less than 0.05 in paired comparison. Platelet half-life (72 +/- 11 before vs. 76 +/- 11 hours after 5 days of co-dergocrine treatment) showed a statistically significant (p less than 0.001) prolongation, whereas in the placebo group no relevant change of T/2 was observed (71 +/- 10 before vs. 72 +/- 10 hours on day 5, p greater than 0.10). No relevant effects on ADP-induced platelet aggregation, platelet-release reaction, platelet aggregate ratio, TXB2 plasma levels and thrombin-induced MDA-formation could be detected. These results indicate that co-dergocrine decreased in-vivo platelet residence time to atherosclerotic lesions of the carotid artery. Co-dergocrine may thereby be of benefit in prevention of mural thrombus formation and prevention of transient ischemic attacks, but also of atherosclerosis in man.
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PMID:Effects of Hydergine on platelet deposition on "active" human carotid artery lesions and platelet function. 281 44

In view of the known association of vascular disease with increasing age, we have conducted an analysis of hemostatic system activity with respect to perturbations induced by aging phenomena. We have utilized an immunochemical assay for prothrombin fragment F1 + 2 to quantify Factor Xa activity upon prothrombin in the plasma of 199 healthy males between the ages of 42 and 80. The levels of F1 + 2 in this population generally increased as a function of age (P less than 0.0001). The metabolic behavior of this marker was determined in 10 individuals greater than 65 yr of age with varying levels of F1 + 2, which ranged from 1.28 to 5.85 nM. The elevations in the concentration of this component were not due to diminished clearance of the fragment. Radio-immunoassays for fibrinopeptide A (FPA) and the protein C activation peptide (PCP) were subsequently employed to measure thrombin activity upon fibrinogen and thrombin-thrombomodulin activity upon protein C, respectively, in 82 members of this population ranging in age from 42 to 80. Significant positive correlations were again observed between increasing age and the level of F1 + 2 (P less than 0.0001) as well as FPA (P less than 0.01) and PCP (P less than 0.002). The results of this cross-sectional study indicate that many apparently normal males of increasing age with normal immunologic levels of antithrombin III and protein C exhibit a biochemical defect that denotes the presence of an acquired prethrombotic state.
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PMID:Aging-associated changes in indices of thrombin generation and protein C activation in humans. Normative Aging Study. 282 64


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