Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma concentration of human lipoprotein(a) [Lp(a)] is correlated with the risk of heart disease. A distinct feature of the Lp(a) particle is the apolipoprotein (a) [apo(a)], which is associated with apoB-100, the main protein component of low-density lipoprotein. We now report that apo(a), which has extensive homology to plasminogen, binds to immobilized fibronectin. The binding of Lp(a) was localized to the C-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) with fibronectin resulted in fragmentation of fibronectin. The cleavage pattern, as visualized by gel electrophoresis and immunoblotting, was reproducibly obtained with Lp(a) purified from five different individuals and was distinct from that obtained upon proteolysis of fibronectin by plasmin or kallikrein. The use of synthetic peptide substrates demonstrated that the amino acid specificity for Lp(a) was arginine rather than lysine. The proteolytic activity of Lp(a) was localized to apo(a) and experiments with inhibitors indicated that the proteolytic activity was of serine proteinase-type.
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PMID:Lipoprotein(a) binds to fibronectin and has serine proteinase activity capable of cleaving it. 253 57

Since infective endocarditis may affect individuals without pre-existing valvar heart disease, and Staphylococcus aureus is the organism most commonly involved, the binding characteristics of S aureus to several components of normal vascular endothelium and subendothelium were studied. S aureus adhered specifically to endothelial monolayers (6.08(1.10)%; p less than 0.005), fibronectin (5.43(0.81)%; p less than 0.001), fibrinogen (7.13(1.43)%; p less than 0.001), and acid soluble calf skin collagen (2.38(0.90)%; p less than 0.001). S aureus also adhered specifically to Von Willebrand factor (1.62(0.28)%, p less than 0.001). Protein A containing (Cowan I) and deficient (Wood) strains of S aureus adhered similarly to all surfaces and substrates (NS). Escherichia coli adhered poorly. Immunofluorescence microscopy of preconfluent endothelial cells identified an extensive pericellular fibronectin network at regions of cell to cell contact. Light microscopy showed S aureus binding solely within these regions. Therefore, the ability of S aureus to infect valvar endothelium may be dependent on the presence of a fibronectin receptor. The existence of specific receptor for S aureus on the endothelial cell surface itself remains undetermined.
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PMID:Bacterial tissue tropism: an in vitro model for infective endocarditis. 328 1

The effects of environmental hyperthermia (exposure to a hot, dry microclimate) on the human body were investigated with particular reference to certain clotting parameters in healthy subjects and patients at risk of thrombosis. The study covered 70 volunteers, 10 of them clinically healthy (6 males and 4 females) aged 37.7 +/- 9.7 and 60 patients at risk of thrombosis aged 18-60 and divided according to pathology as follows: 26 with ischaemic cardiopathy, 22 with metabolic disorders (12 diabetics, 8 with dyslipidaemia, 2 with hyperuricaemia) and 12 with obliterating arteriopathies of the lower extremities (Fontaine stage 2 and 3). The following standardised protocol was adopted: 2 hours exposure in a controlled climate chamber (40 degrees C, 40-50% humidity, standard air speed 4 m/min, barometric pressure 760 mmHg) for a total of 8 exposures (2 per week for 1 month). This approach was adopted in order to assess not only the effect of each single exposure but also the role of any adaptation to heat. Three blood samples were taken from each subject for each session: the first in basal conditions in a comfortable environment, the second at the end of the 2 hour exposure; the third 30 minutes after the end of the session. Simultaneously samples of arterial blood were taken for pH assays and a spleen echography was performed in basal conditions and at the end of the session for each subject. Each blood sample was tested for several parameters essentially attributable to blood concentration for a broader view of the biological effects of exposure to heart (Ht, blood protein, Nat, K+). The clotting factors under specific study were also assessed (platelet count and volume, beta-thromboglobulin, PF4, von Willebrand Factor VIII, thromboxane B2, fibronectin). Body weight, blood pressure and oral temperature were also measured in all subjects before and after each session. In all subjects both healthy and at risk of thrombosis oral temperature increased (1 +/- 0.4 degrees); on average blood pressure was already higher in basal conditions in the patient group; body weight fell by 900 +/- 120 G in both groups. Ht and blood protein increased significantly in both groups while electrolyte changes were insignificant and blood pH showed a tendency towards acidosis. Clotting parameters revealed a tendency towards thrombophilia in all subjects: platelet count and volume were already higher in the patient group in basal conditions and increased after exposure to hyperthermia. Beta-thromboglobulin, FP4, Factor VIII, thromboxane B2 and fibronectin all increased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Influence of high environmental temperature on various parameters of blood coagulation in healthy subjects and in thrombosis risk patients]. 369 44

The cardiac cytoskeleton and the extracellular matrix play an essential role for maintaining cellular integrity and function of the myocardium. The network of microtubules and intermediate filaments are disrupted by the inflammatory reaction which depends on resident cells (myocytes, fibroblasts, endothel cells) and on systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. The inflammation in heart disease and the induction of fibrosis are mediated by cytokines and growth factors derived from fibroblast activation and from the B- and T-cell activity. A possible connecting link for the induction of fibrosis is the presentation of the myocardial antigens to the immune system and its subsequent cellular and humoral autoreactive response (Figure 1). Different autoantibodies to sarcolemmal and myolemmal antigens, to laminin, to extracellular matrix proteins, to the collagens and to myofibrils were demonstrated both in endomyocardial biopsy and as circulating autoantibodies in the peripheral blood. The pathophysiological role of the cytoskeleton and the extracellular matrix are well defined for beta-tubulin, fibronectin, laminin, desmin, vimentin, vinculin and collagen: beta-tubulin is increased or altered in dilated cardiomyopathy (DCM). Fibronectin appears in irregular forms in DCM as well. Ultrastructural analysis showed an increased content of laminin in basement membranes. In addition anti-laminin antibodies were found in 73% of patients with myocarditis and in 78% of patients with DCM. Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. The vimentin of the endothelial cells and the vinculin of the sarcolemmal membrane and the intercalated discs have been demonstrated to be irregularly shaped and increased in content in DCM whereas in myocarditis their appearance and content is still unknown. The intracellular content of collagen type 5 is increased in DCM and in myocarditis. The presence of autoantibodies to components of the cytoskeleton and the extracellular matrix in myocarditis and perimyocarditis is well-described. Antibodies to the myolemma and the sarcolemma are found in almost all patients with perimyocarditis in the serum or bound in the biopsy. Some of them have been known cytolytic in vitro to isolated heart cells. In pericarditis a shift to antibodies to the extracellular matrix, collagen and intermediate filaments is observed among the circulating antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The extracellular matrix and cytoskeleton of the myocardium in cardiac inflammatory reaction]. 777 71

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10). We elucidated the effect of CoQ10 on certain hemostatic parameters that may influence the progression of heart disease. Twelve Yorkshire swine were randomized to receive diet supplementation with either CoQ10 or placebo for 20 days. Blood samples were obtained at baseline and at the end of the feeding period. At the end of the protocol, there were no significant differences in hemostatic parameters in the placebo group. A significant increase in total serum CoQ10 level (from 0.39 +/- 0.06 to 0.96 +/- 0.04 microgram/ml, p < 0.001) was noted after the feeding period in the CoQ10-supplemented group. We observed significant inhibition of ADP-induced platelet aggregation (-9.9%) and a decrease in plasma fibronectin (-20.2%), thromboxane B2 (TXB2, -20.6%), prostacyclin (-23.2%), and endothelin-1 (ET-1, -17.9%) level. There were no changes in the plasma concentrations of the natural antithrombotics [antithrombin-III (AT-III), protein S, and protein C] after CoQ10 supplementation. CoQ10 supplementation in a dose of 200 mg daily is associated with mild antiaggregatory changes in the hemostatic profile. Clinical beneficial effects of CoQ10 may be related in part to a diminished incidence of thrombotic complications.
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PMID:Hemostatic changes after dietary coenzyme Q10 supplementation in swine. 885 71

Closure of the ductus arteriosus requires prenatal formation of intimal cushions, which occlude the vessel lumen at birth. Survival of newborns with severe congenital heart defects, however, depends on ductal patency. We used a gene transfer approach to create a patent ductus arteriosus by targeting the fibronectin-dependent smooth muscle cell migration required for intimal cushion formation. Fetal lamb ductus arteriosus was transfected in utero with hemagglutinating virus of Japan liposomes containing plasmid encoding 'decoy' RNA to sequester the fibronectin mRNA binding protein. Fibronectin translation was inhibited and intimal cushion formation was prevented. We thus established the essential role of fibronectin-dependent smooth muscle cell migration in intimal cushion formation in the intact animal and the feasibility of incorporating biological engineering in the management of congenital heart disease.
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PMID:Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation. 993 Aug 53

The muscle protein myosin binding protein C (MyBPC) is a large multi-domain protein whose role in the sarcomere is complex and not yet fully understood. Mutations in MyBPC are strongly associated with the heart disease familial hypertrophic cardiomyopathy (FHC) and these experiments of nature have provided some insight into the intricate workings of this protein in the heart. While some regions of the MyBPC molecule have been assigned a function in the regulation of muscle contraction, the interaction of other regions with various parts of the myosin molecule and the sarcomeric proteins, actin and titin, remain obscure. In addition, several intra-domain interactions between adjacent MyBPC molecules have been identified. Although the basic structure of the molecule (a series of immunoglobulin and fibronectin domains) has been elucidated, the assembly of MyBPC in the sarcomere is a topic for debate. By analysing the MyBPC sequence with respect to FHC-causing mutations it is possible to identify individual residues or regions of each domain that may be important either for binding or regulation. This review looks at the current literature, in concert with alignments and the structural models of MyBPC, in an attempt to understand how FHC mutations may lead to the disease state.
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PMID:Myosin binding protein C: structural abnormalities in familial hypertrophic cardiomyopathy. 1511 10

The renin-angiotensin system (RAS) and transforming growth factor-beta1 (TGF-beta1) play a pivotal role in the development of cardiac hypertrophy and heart failure. Recent studies indicate that angiotensin II (Ang II) and TGF-beta1 do not act independently from one another but rather act as part of a signalling network in order to promote cardiac remodeling, which is a key determinant of clinical outcome in heart disease. This review focuses on recent advances in the understanding, how Ang II and TGF-beta1 are connected in the pathogenesis of cardiac hypertrophy and dysfunction. Increasing evidence suggests that at least some of the Ang II-induced effects on cardiac structure are mediated via indirect actions. Ang II upregulates TGF-beta1 expression via activation of the angiotensin type 1 (AT1) receptor in cardiac myocytes and fibroblasts, and induction of this cytokine is absolutely required for Ang II-induced cardiac hypertrophy in vivo. TGF-beta induces the proliferation of cardiac fibroblasts and their phenotypic conversion to myofibroblasts, the deposition of extracellular matrix (ECM) proteins such as collagen, fibronectin, and proteoglycans, and hypertrophic growth of cardiomyocytes, and thereby mediates Ang II-induced structural remodeling of the ventricular wall in an auto-/paracrine manner. Downstream mediators of cardiac Ang II/TGF-beta1 networking include Smad proteins, TGFbeta-activated kinase-1 (TAK1), and induction of hypertrophic responsiveness to beta-adrenergic stimulation in cardiac myocytes.
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PMID:TGF-beta1 and angiotensin networking in cardiac remodeling. 1527 67

The epicardium of the heart originates from a cluster of mesothelial-derived cells that develop beneath the sinus venosus in the embryonic day (E) 9.0-9.5 mouse. The subsequent proepicardium-epicardium transition that forms the epicardial layer of epithelial cells covering the myocardial surface is nearly complete by E10.0-E10.5 and results in a fully covered heart by E11.0. In this study, we show that an established model of congenital heart disease, the retinoid X receptor alpha knockout (RXRalpha-/-) embryo, displays a malformed epicardium. At E10.0-E10.5, the RXRalpha-/- has several large regions of myocardium that remain bare. Furthermore, by E11.5-E12.5, when a complete epithelial layer is formed in the mutant, large regions of the epicardium become distended from the underlying myocardium. Close examination of the E9.5 mutant revealed an elevated apoptosis level within the proepicardial cluster of mesothelial cells. Additionally, among the extracellular matrix proteins analyzed, expression of fibronectin was elevated in the RXRalpha-/- as assessed by immunostaining in paraffin-embedded sections and proepicardial explants. We propose that these events contribute to a developmental delay in the formation of the epicardium, which leads to an abnormal epicardium and ultimately contributes to the cardiac malformations seen in the RXRalpha-/-.
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PMID:Analysis of the proepicardium-epicardium transition during the malformation of the RXRalpha-/- epicardium. 1586 8

Myocardial tissue engineering presents a potential treatment option for heart disease. Cardiomyocytes isolated at various stages of development retain the ability to form contractile networks in vitro, which suggests that it should be possible to reconstitute viable myocardium given the appropriate architecture, stimuli, and cardiomyogenic cell source. This study investigates the effects of modifying substrate surface energy (by plasma etching) and protein coating (by fibronectin adsorption) on neonatal rat ventricular myocyte (NRVM) function. Primary NRVMs were cultured for 96 h on modified and control films of a common degradable polymer, polylactide-co-glycolide. Cultures were analyzed for cell spreading, protein content, and mRNA expression of atrial natriuretic factor and beta-myosin heavy chain. The results demonstrate that NRVMs cultured on etched films significantly increased in spreading, myofibril development, protein content, and gene expression of atrial natriuretic factor and beta-myosin heavy chain compared with unetched films, and that this surface energy effect is overwhelmed by the addition of fibronectin. Conclusions from this study are that surface energy and protein adsorption influence the gene expression of adherent NRVMs, and may be important for modulating the function of engineered myocardium.
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PMID:Modulation of gene expression in neonatal rat cardiomyocytes by surface modification of polylactide-co-glycolide substrates. 1597 94


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