Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) is a selective and careful apheresis procedure. Through the application of heparin and lowering the pH value, lipoproteins and fibrinogen are reduced by 50-60%. In addition, adhesion molecules (ICAM-1, VCAM-1, p-selectin) which play a key role in the development and progression of atherosclerosis, are also markedly reduced. A PET scan performed 20 h after LDL apheresis shows the improvement of coronary vasodilation capacity. This is supposed to be mainly due to the marked reduction of LDL cholesterol and fibrinogen with consecutive improvement of endothelial dysfunction and rheology.
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PMID:Heparin-induced extracorporeal low-density lipoprotein precipitation. 1292 14

The prolonged administration of either heparin or dicoumerol has been demonstrated to be effective in retarding the formation of atheromata in the cholesterol-fed chick. This beneficial action is possibly produced as a result of a demonstrated antihypercholesteremic action exerted by these anticoagulants. Heparin is ineffective in preventing the marked turbidity of sera from cholesterol-fed chickens. After the formation of atherosclerosis in the chick neither heparin nor dicoumerol is effective in hastening the regression of this condition. The serum lipid picture as well as the degree of atheroma of the various groups in the regression experiments is unaffected by the anticoagulants.
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PMID:The influence of anticoagulants on the formation and regression of experimental atherosclerosis. 1320 15

Sodium spirulan (Na-SP) is a sulfated polysaccharide with M(r) approximately 220,000 isolated from the blue-green alga Spirulina platensis. The polysaccharide consists of two types of disaccharide repeating units, O-hexuronosyl-rhamnose (aldobiuronic acid) and O-rhamnosyl-3-O-methylrhamnose (acofriose) with sulfate groups, other minor saccharides and sodium ion. Since vascular smooth muscle cell proliferation is a crucial event in the progression of atherosclerosis, we investigated the effect of Na-SP on the proliferation of bovine arterial smooth muscle cells in culture. It was found that Na-SP markedly inhibits the proliferation without nonspecific cell damage. Either replacement of sodium ion with calcium ion or depolymerization of the Na-SP molecule to M(r) approximately 14,700 maintained the inhibitory activity, however, removal of sodium ion or desulfation markedly reduced the activity. Heparin and heparan sulfate also inhibited vascular smooth muscle cell growth but their effect was weaker than that of Na-SP; dextran sulfate, chondroitin sulfate, dermatan sulfate and hyaluronan failed to inhibit the cell growth. The present data suggest that Na-SP is a potent inhibitor of arterial smooth muscle cell proliferation, and the inhibitory effect requires a certain minimum sequence of polysaccharide structure whose molecular conformation is maintained by sodium ion bound to sulfate group.
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PMID:Sodium spirulan as a potent inhibitor of arterial smooth muscle cell proliferation in vitro. 1499 20

This study investigates a stent-less local delivery system for anti-restenotic agents utilizing antibodies to cross-linked fibrin (XLF). Heparin and low molecular weight heparin (LMWH) were conjugated to an antibody to cross-linked fibrin D-dimer (1D2). Rabbit right carotid arteries were injured with a balloon catheter, then the animals were given a bolus injection of 40 microg/kg 1D2-heparin (26-70 microg/kg heparin) or 1D2-LMWH (29-80 microg/kg LMWH) conjugates or controls of saline (0.5 ml/kg), heparin (150 U/kg), LMWH (2 mg), or 1D2 (40 microg/kg), with or without a heparin bolus and sacrificed after 2 weeks (8 groups, n = 6/group). The injured artery of rabbits given 1D2-heparin or 1D2-LMWH conjugates had reduced neointimal development, with decreased luminal narrowing and positive remodelling compared with animals given control drugs. Animals given 1D2-heparin conjugate (with a heparin bolus) had three to five times more endothelial cells than the rabbits given saline or unconjugated heparin, while rabbits given 1D2-LMWH conjugate had up to 59% fewer neointimal cells than those given unconjugated drugs. There was little difference in extracellular matrix organization or composition. Thus cross-linked fibrin-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall where they influence wall remodelling and endothelial and neointimal cell number, reducing neointimal formation without systemic complications. Local delivery of anti-restenotic agents should minimise systemic effects, bleeding complications and potentially the cost of treatment due to a single, lower dose.
Atherosclerosis 2004 Sep
PMID:Targeted delivery of heparin and LMWH using a fibrin antibody prevents restenosis. 1530 77

This paper analyzes the results of the use of enoxaparin for anticoagulant therapy in reconstructions on the ascending aorta (AA) as compared to unfractionated heparin applied previously in the control group. Between 1986 and 2003 a total of 30 patients with AA aneurysms were operated on at the clinic. Insufficiency of the aortic valve with degree II-III regurgitation was present in 25 (83.3%) cases. Chronic dissection of the AA was identified in 10 (33.3%) cases. The patient's age varied from 24 to 52 years (mean 39 years). The etiological factors of AA aneurysm were: Marfan's syndrome (46.7% of cases), Erdheim's syndrome (26.7%), atherosclerosis (10.0% of cases); previous chest traumas were recognized in 16.6% of patients. All the patients were operated on under extra-corporeal circulation and moderate hypothermia. The patients were distributed into two groups. In the control group, eighteen patients were operated on. Anticoagulant therapy was carried out using unfractionated heparin i. v. in a daily dose 10-15 thousand units. Heparin injection was initiated on the first postoperative day and continued for 6.5 days on the average, with a progressive change over to the use of indirect anticoagulants. In the basic group, twelve operated patients were administered the anticoagulant enoxaparin s.c. in a daily dose 0.7-1.0 mg/kg bw. Enoxaparin therapy was initiated from the first postoperative day and continued for 8.9 days on the average, with a progressive change over to indirect anticoagulants. The postoperative lethality in the control group accounted for 22.2% (4 patients). In two cases, it was induced by heart failure and in two cases, by hemorrhagic complications. In the basic group, the beneficial results were achieved in 91.7%; no hemorrhagic complications were recorded. The data obtained allow the conclusion that the use of enoxaparin significantly facilitates the postoperative management of patients with AA aneurysms, providing for a controllable and safe anticoagulant effect.
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PMID:[The use of low-molecular heparins in reconstructive surgery of ascending aortic aneurysms]. 1562 90

Uncontrolled proliferation of vascular smooth muscle cells (VSMCs) contribute to intimal hyperplasia during atherosclerosis and restenosis. Heparin is an antiproliferative agent for VSMCs and has been shown to block VSMC proliferation both in tissue culture systems and in animals. Despite the well documented antiproliferative actions of heparin, its cellular targets largely remain unknown. In an effort to characterize the mechanism of the antiproliferative property of heparin, we have analyzed the effect of heparin on cell cycle in VSMC. Our results indicate that the heparin-induced block in G(1) to S phase transition is imposed by p27(kip1)-mediated inhibition of cyclin-dependent kinase 2 activity. Further analysis of p27(kip1) mRNA levels showed that the increase in p27(kip1) protein levels in heparin-treated VSMC occurs at posttranscriptional levels. We present evidence that heparin causes stabilization of p27(kip1) protein during G(1) phase and thereby prevents activation of cyclin-dependent kinase 2.
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PMID:Regulation of vascular smooth muscle proliferation by heparin: inhibition of cyclin-dependent kinase 2 activity by p27(kip1). 1573 Nov 13

Heparin binding-epidermal growth factor-like growth factor (HB-EGF) is one of the EGF receptor ligands and possesses several functional domains. It is involved in diverse biological processes, including wound healing, blast implantation, atherosclerosis and tumor formation, through its interactions with various molecules. We have reported that HB-EGF gene expression is significantly elevated in human ovarian cancer, and further demonstrated that HB-EGF plays key roles in the acquisition of malignant phenotypes, such as cell survival in peritoneal fluid, cell adhesion on extracellular matrices, invasion, angiogenesis, tumorigenicity, and chemoresistance in ovarian cancer. Thus, HB-EGF was considered as a promising target for cancer therapy. In vitro as well as in vivo experiments have revealed that cross-reacting material 197 (CRMI97), a specific inhibitor of HB-EGF, or a small interfering RNA for HB-EGF can block each step involved in peritoneal dissemination. According to these pieces of evidence, the development of targeting tools against HB-EGF, such as CRM197, could allow us to improve the prognosis of cancer patients.
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PMID:New approach to cancer therapy: heparin binding-epidermal growth factor-like growth factor as a novel targeting molecule. 1797 33

Heparin-Binding Epidermal Growth Factor (HB-EGF) is growth factor member of EGF family that stimulate differentiation and growth. HB-EGF was initially identified as a secreted product of human macrophage-like cells, it is sinthetized as a transmembrana protein; proHB-EGF; that is shed by specific metalloproteases, releasing soluble growth factor(sHB-EGF). It exerts biological activity trough activation of the EGFR. sHB-EGF is implicated in diverse biological processes: angiogenesis, shin wound, blastocysts implantation, atherosclerosis, tumor formation moreover it acts as the Diphtheria Toxin (DT) receptor. HB-EGF It's an important molecule because could be a novel targeting for cancer and atherosclerosis therapy.
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PMID:[Heparin-binding epidermal growth factor (HB-EGF): myth or reality?]. 1846 70

Myeloperoxidase (MPO), a heme protein abundantly expressed and secreted by polymorphonuclear neutrophils (PMN), has emerged as a critical mediator in coronary atherosclerosis. Retrospective analyses have suggested that free plasma levels of MPO predict adverse outcome in patients with low troponin T (TnT) levels who subsequently experience myocardial injury. The aim of this study was to evaluate the time course of MPO plasma levels in the early stages of acute myocardial infarction (AMI). Of 155 consecutive patients hospitalized for acute coronary syndromes, 38 presenting within 2 h of the onset of symptoms and subsequently diagnosed for AMI were included in the study. Serial blood samples taken between 1 and 24 h after the onset of chest pain were analyzed for MPO, TnT, creatine kinase MB, myoglobin, and high sensitive C-reactive protein. Fifty patients with angiographically proven but stable coronary artery disease (CAD) served as controls. In contrast to all other investigated markers, MPO was markedly elevated within 2 h of symptom onset in patients with AMI. Heparin, which is known to increase MPO plasma levels in patients with stable CAD, had no effect on MPO plasma levels in AMI patients. High levels of MPO plasma levels at the time of admission and the rapid peak of free plasma MPO levels after the onset of symptoms suggests that PMN activation is an early event in AMI and potentially precedes myocardial injury.
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PMID:Neutrophil activation precedes myocardial injury in patients with acute myocardial infarction. 1936 43

It was nearly 100 years since heparin was discovered, but the role of this widely used anticoagulant is still remarkably thought provoking now. During pathological processes such as atherosclerosis, inflammation, cancer and infection, phenomena of cell adhesion are ubiquitous and complicated. Heparin exerts anti-adhesion activity appearing as a common mechanism of its potential polypharmacology in those diseases. Furthermore, heparin can bind a variety of signalling molecules such as growth factors, cell surface proteins of pathogens and most notably, cell adhesion molecules. These signalling molecules are involved in cell communication, acting as ligands, receptors and second messengers. Considering that heparan sulphate glycosaminoglycan is increasingly recognized as a key mediator in many cellular processes, the structural similarity with heparan sulphate suggests that heparin is a multifunctional intervenor in cell communication.
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PMID:Heparin: an intervenor in cell communication. 1965 57


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