Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein(a) (Lp[a]) can be defined as a lipoprotein particle having as a protein moiety apolipoprotein B-100 (the protein associated with low-density lipoprotein) disulfide-linked to apolipoprotein(a), the distinctive glycoprotein of Lp(a) that is homologous to plasminogen. Several forms of Lp(a) occur in the circulation. This polymorphism is related to the apolipoprotein(a) size heterogeneity that is controlled by the several alleles of the apolipoprotein(a) gene. High plasma levels of Lp(a) have been correlated with an increased risk for atherothrombotic cardiovascular disease by a mechanism that is as yet undefined. Pathogenicity may also derive from Lp(a) particles that have been modified by events believed to occur when Lp(a), after traversing the artery endothelium, reaches the intima. Aside from several promising leads, there are no universally accepted ways to lower high plasma Lp(a) levels. At this time, it is best to target efforts toward the modifiable risk factors by using appropriate diets and exercise programs and, whenever necessary, drug therapy.
 ...
PMID:Lipoprotein(a). A genetic risk factor for premature coronary heart disease. 153 88

We have previously shown that tobacco glycoprotein (TGP), a polyphenol-rich glycoprotein isolated from tobacco or from cigarette smoke, affects the immune system. In this study we show that TGP induces human PBL and adherent cells to produce IL-1 alpha and IL-1 beta. Two peaks of IL-1 activity were observed; one at 18-24 h, the second at 4-6 d after initiation of culture. A similar pattern was observed for the steady state level of IL-1 mRNA. These data suggest that the production of IL-1 by cells stimulated with TGP might be a factor in cardiovascular disease associated with cigarette smoking.
 ...
PMID:Two peaks of interleukin 1 expression in human leukocytes cultured with tobacco glycoprotein. 278 83

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 implication of HDL as a negative risk factor in cardiovascular disease has focused on the need for an accurate but rapid routine method for determining HDL-cholesterol in human serum. A practical approach is the specific precipitation of apo-B-containing lipoproteins (atherogenic lipoproteins) by Concanavalin A (Con. A), a lectin with high affinity for glycoprotein apo-B. Specificity was assessed by radial immunodiffusion of apoprotein B in whole serum and in Con. A supernates. Double-immunodiffusion of isolated LP-fractions against anti-apo-B and Con. A demonstrated immunochemical identity of Con. A precipitable LP with apo-B-containing LP. Con. A precipitated cholesterol in the d : 1.063-1.21 g/ml fraction when apo-B was present. Complete precipitation of low density cholesterol was demonstrated, using a reconstituted serum sample radiolabelled in the d less than 1.063 g/ml fraction. Treatment of a reconstituted serum sample containing radiolabelled 125I-apo-A-I with Con. A demonstrated precipitation of trace amounts only of apo A-I. Con. A precipitated LP-B cholesterol quantitatively even when serum triglycerides (TG) exceeded 37.7 mmol/l. Clinical application of this method revealed that 73% of the patient population demonstrated apo-B in the d greater than 1.063 g/ml fraction.
 ...
PMID:Evaluation of a new precipitation procedure for estimating high density lipoprotein cholesterol: precipitation of apolipoprotein B associated cholesterol with concanavalin A. 732 24

The well documented association between high plasma levels of lipoprotein(a) (Lp(a)) and cardiovascular disease might be mediated by the lysine binding of apolipoprotein(a) (apo(a)), the plasminogen-like, multikringle glycoprotein in Lp(a). We employed a mutational analysis to localize the lysine-binding domains within human apo(a). Recombinant apo(a) (r-apo(a)) with 17 plasminogen kringle IV-like domains, one plasminogen kringle V-like domain, and a protease domain or mutants thereof were expressed in the human hepatocarcinoma cell line HepG2. The lysine binding of plasma Lp(a) and r-apo(a) in the culture supernatants of transfected HepG2 cells was analyzed by lysine-Sepharose affinity chromatography. Wild type recombinant Lp(a) (r-Lp(a)) revealed lysine binding in the range observed for human plasma Lp(a). A single accessible lysine binding site in Lp(a) is indicated by a complete loss of lysine binding observed for r-Lp(a) species that contain either a truncated r-apo(a) lacking kringle IV-37, kringle V, and the protease or a point-mutated r-apo(a) with a Trp-4174-->Arg substitution in the putative lysine-binding pocket of kringle IV-37. Evidence is also presented for additional lysine-binding sites within kringles 32-36 of apo(a) that are masked in Lp(a) as indicated by an increased lysine binding for the point mutant (Cys-4057-->Ser), which is unable to assemble into particles. An important role of these lysine-binding site(s) for Lp(a) assembly is suggested by a decreased assembly efficiency for deletion mutants lacking either kringle 32 or kringles 32-35.
 ...
PMID:Identification of two functionally distinct lysine-binding sites in kringle 37 and in kringles 32-36 of human apolipoprotein(a). 789 Jul 60

Electron cryomicroscopy was used to study the structure of human lipoprotein(a) (Lp(a)), a plasma lipoprotein implicated in cardiovascular disease. An individual Lp(a) particle consists of a neutral lipid core within a shell of phospholipid, cholesterol and glycoprotein. In principle, electron cryomicroscopy images of single particles should contain structural detail attributable to the density differences among these components and the surrounding buffer. We observed such structural detail in images of frozen, hydrated Lp(a) particles. Lp(a) particles appeared to be roughly spherical in shape with an average diameter of 210 A. As is generally true for unstained samples in vitreous ice, imaged with a low electron dose, these images have low contrast with low signal-to-noise ratios. To increase the signal-to-noise ratio, we averaged classes of similar particles. We began with a set of 5813 randomly oriented Lp(a) particles and generated classes using a linear multivariate statistical method, followed by hierarchical ascendant classification. Our initial classification, based on only the first eight eigenvectors, separated particles on the basis of gross size and shape. After a rough reference-free alignment step, a second classification used the finer details in the images. This approach yielded class averages with structural detail only faintly visible in the raw, single images.
 ...
PMID:Electron cryomicroscopy and digital image processing of lipoprotein(a). 818 47

Alterations in the rate and pattern of cell movement are prominent features of many human diseases, including inflammation, cardiovascular disease and cancer. The ability to regulate the interactions of cells with each other and with adhesion factors in extracellular matrices therefore offers a novel approach to the treatment of these diseases. The intention of this article is to provide an overview of the role of the adhesive glycoprotein fibronectin and its receptors in the adhesive behavior of tumors, to review ongoing work that is aimed at developing agents with the ability to regulate adhesion to fibronectin, and to highlight aspects of the malignant phenotype that are potential targets for intervention with such agents.
 ...
PMID:Fibronectin and cancer: rationales for the use of antiadhesives in cancer treatment. 825 80

Recent advances have resulted in the elucidation of the principal molecular pathways of platelet function. Parallel studies have led to the identification of glycoprotein antigens whose presence at the platelet surface indicates an activated state. Such markers include GMP-140 and other glycoproteins of intracellular membranes whose translocation requires secretion and fusion of granule membranes with those joined to the surface. Other markers include activation-dependent epitopes on the GP IIb-IIIa complex and adhesive proteins bound to the activated GP IIb-IIIa receptor. Such epitopes can be detected by specific monoclonal antibodies. Quantification of their binding by flow cytometry allows an estimation of epitope expression within the whole platelet population. Our studies are designed to answer the question of whether measuring these epitopes is useful for predicting thrombosis in patients with acute cardiovascular disease. For this, we have examined three states where platelet function may be modified and where the risk of thrombosis and/or bleeding is increased. These include (i) patients with severe burns, (ii) patients who have undergone coronary angioplasty, and (iii) patients receiving fibrinolytic therapy following myocardial infarction. Our results show that activated platelets can be detected in the circulation and that their level reflects the degree of the lesion. Nonetheless, we have as yet failed to show a direct correlation between their presence and a future pathological event.
 ...
PMID:Platelet activation in thrombotic disorders. 851 Oct 43

Factor VII (FVII) is a plasma vitamin K-dependent glycoprotein that plays an important role in the initiation of tissue factor-induced coagulation (extrinsic pathway of blood coagulation). An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. Recently, the coagulation assay using soluble tissue factor(sTF) enables us to measure the plasma levels of the activated form of factor VII(FVIIa) without the effect of the FVII zymogen form. We have developed the fluorogenic assay for FVIIa using sTF and measured the plasma FVIIa in atherosclerotic diseases. The FVIIa level in the Japanese was lower than that reported in Caucasians, suggesting that the incidence of ishemic heart disease is lower in the former. The FVIIa level was higher in the patients with cardiovascular diseases (ischemic heart disease and cerebral infarction), non-insulin-dependent diabetic mellitus, hypertension with microalbuminuria, and renal failure than in the healthy controls. The FVIIa levels were also increased in non-insulin-dependent diabetic patients, and this FVIIa increase was positively correlated with urinary albumin excretion. Furthermore, FVIIa levels were not correlated with the levels of lipids and the activity of hepatic synthesis, indicating that FVIIa may be an independent risk factor for cardiovascular disease.
 ...
PMID:[Activated factor VII as a new cardiovascular risk factor of atherothrombotic disease]. 856 29

Hemopexin, a heme-binding serum glycoprotein, is thought to play an important role in the prevention of oxidative damage that may be catalysed by free heme. Through the use of EPR techniques, the generation of free radicals from organic hydroperoxides by heme and heme-hemopexin complexes, and the concomitant formation of high oxidation-state iron species has been studied; these species are implicated as causative agents in processes such as cardiovascular disease and carcinogenesis. From the rates of production of these species from both n-alkyl and branched hydroperoxides, it has been inferred that the dramatic reduction in the yield of oxidising species generated by heme upon its complexation with hemopexin arises from steric hindrance of the access of hydroperoxide to the bound heme.
 ...
PMID:EPR studies on the effects of complexation of heme by hemopexin upon its reactions with organic peroxides. 857 50


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