UMLS:C0007222 - FACTA Search

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Query: UMLS:C0007222 (cardiovascular disease)
65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, alpha(1)-acid-glycoprotein (AAG), alpha(1)-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.
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PMID:Systemic inflammation in cardiovascular and periodontal disease: comparative study. 1187 89

The central role played by the alphaIIb beta3 receptor in platelet aggregation, and hence in platelet thrombosis, has led to the development of a number of parenteral and oral glycoprotein (GP) IIb/IIIa inhibitors for use in cardiovascular disease states, such as acute coronary syndromes and stroke. The predominant effect of these agents is to inhibit platelet aggregation, although studies of alphaIIb beta3 receptor function and various GP IIb/IIIa inhibitors have demonstrated the potential for these agents to produce effects on other aspects of platelet function, in addition to non-platelet effects. Overall, clinical studies have demonstrated an impressive beneficial effect for parenteral agents in reducing ischemic complications following percutaneous intervention, and a more modest beneficial effect in the treatment of patients with acute coronary syndromes. Trials with oral GP IIb/IIIa inhibitors in similar patient populations have demonstrated toxicity, manifested by an increased mortality in treated patients. Increased understanding of molecular aspects of both alphaIIb beta3 receptor function and the effects of GP IIb/IIIa inhibition may help explain some of the inconsistency in recently reported clinical studies with parenteral agents, and the frank toxicity of oral agents. Such studies may also hold the key to the development of newer agents with enhanced therapeutic benefit.
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PMID:Glycoprotein IIb/IIIa antagonists--from bench to practice. 1196 26

There is a significant association between cardiovascular disease and depression. Previous studies have documented changes in platelets in depression. It is unknown if depression causes functional changes in platelet surface receptors. Therefore, we analyzed (1) the surface expression of glycoprotein (GP)Ib and the integrin receptor alpha(IIb)beta(IIIa), receptors involved in platelet adhesion and aggregation, (2) CD62 (P-selectin) and CD63, integral granule proteins translocated during platelet activation, (3) platelet aggregation in response to ADP and (4) plasma levels of glycocalicin and von Willebrand factor (vWF), in depressed patients compared to healthy volunteers. Fifteen depressed patients with a Hamilton depression score of at least 22 and fifteen control subjects were studied. Platelets were assessed for surface expression levels of GPIb, alpha(IIb)beta(IIIa), CD62 and CD63 by flow cytometry. Genomic DNA was isolated to investigate a recently described polymorphism in the 5' untranslated region of the GPIbalpha gene. The number of GPIb receptors was significantly increased on the surface of platelets from patients with depression compared to control subjects. Surface expression of CD62 was also significantly increased in the depressed patients versus control subjects. There was no significant difference between depressed patients and healthy volunteers in the surface expression of alpha(IIb)beta(IIIa) or CD63, or in glycocalicin or vWF plasma concentration, or ADP-induced aggregation. There was no difference in allele frequency of the Kozak region polymorphism of the GPIbalpha gene, which can affect GPIb expression. The results of this study demonstrate that the number of GPIb receptors on platelets are increased in depression and suggest a novel risk factor for thrombosis in patients with depression.
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PMID:Depression is associated with an increase in the expression of the platelet adhesion receptor glycoprotein Ib. 1200 98

Apolipoprotein D (APOD, gene; apoD, protein) is a plasma high-density lipoprotein (HDL)-associated glycoprotein, with a putative role in the cholesterol (CHOL) transport pathway. An apoD protein polymorphism has been previously reported by us. The cathodically shifted pattern seen on isoelectric focusing gels, controlled by the APOD*2 allele, was found to be unique to populations of African ancestry. To characterize the molecular basis of the protein polymorphism and to identify new mutations, we used a combination of SSCP, DHPLC and DNA sequencing techniques to screen the entire coding region of the APOD gene. We identified three distinct missense mutations, including Phe36Val, Tyr108Cys, and Thr158Lys with frequencies ranging from 2.1 to 2.8% in 722 African blacks from Nigeria. In addition, a common 8 bp deletion polymorphism was observed in intron 1 with a carrier frequency of 30.1%. The missense mutation, Thr158Lys correlated with the APOD*2 allele of the protein polymorphism. None of the 454 Caucasians screened for these polymorphisms showed any variation. We also determined the effect of these polymorphisms on plasma lipid levels in the African black population by generalized linear model (GLM). The Val36 allele was associated with significantly decreased HDL3-C (P=0.027) and apoA-I (P=0.030) levels among females. The Lys158 allele was associated with significantly increased Lp(a) (P=0.018) and triglyceride (P=0.017) levels, among females and males, respectively. In addition, males heterozygous for both intron 1 and codon 108 polymorphisms showed significantly increased HDL-C (P=0.011), HDL3-C (P=0.041), HDL2-C (P=0.009), apoA-I (P=0.005) and decreased LDL-C (P=0.025) levels. The results of our study show that the APOD gene harbors several polymorphisms, which are unique to African populations. Further study of these polymorphisms may help to characterize the role of apoD in lipid metabolism, and in cardiovascular disease among African populations.
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PMID:Genetic variation in the apolipoprotein D gene among African blacks and its significance in lipid metabolism. 1205 80

CHO cell-elongating factor (Cef) is a recently identified putative virulence factor of Vibrio cholerae. Our previous studies show that this 85 kDa protein elongates CHO cells, causes fluid accumulation in suckling mice and has esterase activity. In this study, the cef gene was cloned in Escherichia coli using a yeast vector and subsequently expressed in the yeast Pichia pastoris. The cef genes from V. cholerae candidate vaccine strains JBK 70 and CVD 103-HgR were sequenced and found to be nearly identical (100 and 99.9% respectively) with an open reading frame (ORF) from the published sequence of V. cholerae N16961. Cloned toxin was purified to homogeneity in 3 steps using anion exchange, hydrophobic interaction and gel filtration chromatography. The size of cloned Cef on SDS-PAGE gels was 114 kDa. The increased size was probably due to glycosylation by the yeast since cloned protein reacted strongly with a glycoprotein stain. The cloned protein could not be directly sequenced, but when treated with trypsin, yielded a protein fragment with an amino acid sequence that matched the sequence predicted for the Cef protein. The purified cloned protein had esterase and CHO cell activity, but no suckling mouse activity.
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PMID:Cloning, expression and characterization of the CHO cell elongating factor (Cef) from Vibrio cholerae O1. 1207 6

Platelet adhesion to a damaged blood vessel is the initial trigger for arterial hemostasis and thrombosis. Platelets adhere to the subendothelium through an interaction with von Willebrand factor (VWF), which forms a bridge between collagen within the damaged vessel wall and the platelet receptor glycoprotein Ib/V/IX (GPIb), an interaction especially important under high shear conditions[1]. This reversible adhesion allows platelets to roll over the damaged area, which is then followed by a firm adhesion mediated by the collagen receptors (alpha(2)beta(1), GPVI, ) in addition[2] resulting in platelet activation. This leads to the conformational activation of the platelet alpha(IIb)beta3 receptor, fibrinogen binding and finally to platelet aggregation. Over the past decades, modulation of platelet function has been a strategy for the control of cardiovascular disease. Lately, drugs have been developed that target the fibrinogen receptor alphaIIbbeta3 or the ADP receptor and many of these promising compounds have been tested in clinical trials. However the development of products that interfere with the first step of hemostasis, i.e. the platelet adhesion, has lagged behind. In this review we want to discuss (i) the in vivo studies that were performed with compounds that target proteins involved in different adhesion steps i.e. the VWF-GPIb-axis, the collagen-VWF axis and the collagen-collagen receptor axis and (ii) the possible advantages these putative new drugs could have over the current antiplatelet agents.
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PMID:Inhibition of platelet adhesion to collagen as a new target for antithrombotic drugs. 1276 39

The objective of this study was to find the changes in glycoprotein composition in both diabetic and non-diabetic patients with and without cardiovascular complications. The study was carried out in Ziauddin Medical University Karachi, Pakistan. Eighty-three patients and control subjects were selected. Among them twenty-one were diabetic patients without any clinical evidence of chronic diabetic complications, twenty-one were diabetic patients with cardiovascular complications, twenty were non-diabetic patients with cardiovascular complications and twenty-one apparently normal, age, sex and weight matched control subjects were investigated. All these patients were selected on clinical grounds from National Institute of Cardiovascular Disease, Karachi. Fasting plasma glucose was increased in all diabetic patients and correlated significantly with and without cardiovascular complications. Fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein and its fractions were increased in diabetic patients with and without cardiovascular complications. Fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid and hexosamine were not different in diabetic patients with cardiovascular complications and diabetic patients without chronic complications as compared with control subjects. In conclusion, fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum proteins and its fractions were increased in diabetic patients with and without complications, but these parameters remained within normal limits in non-diabetic patients with cardiovascular complications.
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PMID:Changes in glycosylated proteins in diabetic and non-diabetic patients with and without cardiovascular complications. 1450 90

Cyclosporine (CyA) has been implicated to increase cardiovascular morbidity and mortality after renal transplantation. Impairment of the fibrinolytic system is one factor involved in the development of thrombotic complications. The aim of this study was to compare hematological and hemostatic parameters among patients on CyA, azathioprine, and prednisone (n = 31) versus CyA and steroids (n = 14). Using commercially available kits we evaluated thrombin activity as thrombin-antithrombin complexes (TAT), prothrombin fragments (1 + 2), thrombin activatable fibrinolysis inhibitor-(TAFI), TAFI activator, thrombomodulin (TM)-a marker for endothelial cell injury,-plasmin generation (plasmin-antiplasmin complex PAP), a glycoprotein linking coagulation and fibrinolysis. We observed that patients not treated with azathioprine displayed longer prothrombin times and activated partial thromboplastin times; higher fibrinogen, platelet counts and fibrinolytic activity index (FAI); shorter euglobulin clot lysis time; as well as lower thrombin generation markers namely, prothrombin fragments 1 + 2 and thrombin-antithrombin complexes. Although patients in the non-AZA group tended to have been engrafted for a longer time (P =.086), the groups did not differ with regard to age, BMI, erythrocyte count, hematocrit, leukocyte count, creatinine clearance, alanine and asparagine aminotransferase activities mean arterial blood pressure, fibrinogen, TAFI, thrombomodulin, or plasmin-antiplasmin complexes. These findings suggest that kidney transplant recipients on triple therapy are at greater risk of cardiovascular disease than those without azathioprine treatment, despite the lower fibrinolytic activity.
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PMID:Some aspects of hemostasis in kidney transplant recipients maintained on cyclosporine, azathioprine, and prednisone in comparison to patients treated with cyclosporine and prednisone. 1469 44

Despite rapid improvement in dialysis technology during the last 20 years the mortality rate is still very high in patients with end-stage renal disease (ESRD), and is in fact comparable to that of many cancer patients with metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD), and cardiac mortality for dialysis patients aged 45 years or younger is more than 100-fold greater than in the general population. Recent evidence suggests that the high cardiovascular mortality rate in this patient population is associated with extensive vascular and valvular calcification. Although hyperphosphatemia may be the major cause of vascular calcification in this patient group it has been suggested that chronic inflammation also contributes to this process. Indeed, recent evidence suggests that inflammatory mediators, such as pro-inflammatory cytokines and adipocytokines, may promote vascular calcification in vitro. Moreover, a2-Heremans Schmid glycoprotein (fetuin), an intrinsic inhibitor of the calcification process, is down-regulated during chronic inflammation. Lower levels of fetuin have recently been found to predict mortality in ESRD. Thus, further studies are needed to elucidate the roles of calcium-free phosphate binders as well as focused anti-inflammatory treatment strategies in the prevention of vascular and valvular calcification in ESRD.
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PMID:[Why do patients with kidney diseases end up with a heart of stone? Disturbances in calcium-phosphate balance and chronic inflammation important causes]. 1471 5

Accumulating evidence suggests that several polymorphisms in factors regulating blood coagulation, platelet function, and lipid metabolism are relevant for susceptibility to ischemic cerebrovascular diseases (CVD). The present study analyzed 15 genetic polymorphisms possibly associated with atherosclerosis and thrombosis in a case-control study involving a total of 200 genetically unrelated Japanese patients with ischemic CVD (mean age 58.3 +/- 7.6 y) and 281 age- and gender-matched control subjects (59.0 +/- 4.1 y). Control subjects were randomly selected from unrelated donors with no history of documented CVD or any type of cardiovascular disease with normal resting electrocardiograms. Among the factors genotyped, two factors, platelet glycoprotein (GP) Ib alpha (Thr145Met) and NADPH oxidase p22phox (His72Tyr), were significantly associated with CVD after adjustment for acquired risk factors including hypertension, diabetes mellitus, hyperlipidemia, and smoking. For those with age < 60 y, 10.6% of the CVD patients and 2.9% of the control subjects had both of the two risk genotypes (GPIb alpha 145Met and p22phox 72Tyr, p < 0.05). The mean onset-age of CVD was 58.6 +/- 7.7 y for those having no or only one risk genotype, while 53.3 +/- 5.5 y for those having both of the risk genotypes (p < 0.05). Thus, GPIb alpha 145Met and p22phox 72 Tyr are the genetic factors associated with the risk of ischemic CVD in the Japanese. Carrying both of the two mutations might be associated with developing CVD at a younger age.
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PMID:[Genetic risk factors for ischemic cerebrovascular disease--analysis on fifteen candidate prothrombotic gene polymorphisms in the Japanese population]. 1496 55

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