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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular smooth muscle cell proliferation is regarded as a key early event in the pathogenesis of atherosclerosis. Heparin-binding growth factor (HBGF)-1 and HBGF-2, also referred to as acidic and basic fibroblast growth factor, are potent mitogens for human vascular smooth muscle cells. These cells coexpress HBGF-1 and HBGF-2 and thus represent a vessel wall source for both polypeptides. In this report, we demonstrate that HBGF-1 and HBGF-2 expression is increased when quiescent human smooth muscle cells are treated with fetal bovine serum. The kinetics of HBGF-1 and HBGF-2 mRNA accumulation following serum treatment are distinct. In addition, HBGF-1 transcripts remain elevated for a longer time period; this may reflect the different decay rates of the HBGF-1 and HBGF-2 mRNAs. Serum-inducible HBGF-1 and HBGF-2 mRNA expression does not occur when RNA synthesis is repressed by actinomycin D but can occur in the presence of cycloheximide, an inhibitor of protein synthesis. Immunoprecipitation experiments indicate that serum treatment also increases HBGF-1 and HBGF-2 production. Smooth muscle cells treated with phorbol 12-myristate 13-acetate or certain combinations of polypeptide growth factors also express increased levels of HBGF-1 and HBGF-2 transcripts. Potential sources for these growth factors in vivo include platelets, macrophages, and T lymphocytes; thus, smooth muscle cells located at sites of vascular injury or inflammation may express elevated levels of HBGF-1 and HBGF-2.
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PMID:Serum, phorbol ester, and polypeptide mitogens increase class 1 and 2 heparin-binding (acidic and basic fibroblast) growth factor gene expression in human vascular smooth muscle cells. 172 53

Restenosis after successful percutaneous transluminal coronary angioplasty is the major clinical problem limiting the long-term efficacy of this treatment for coronary atherosclerosis. Recent advances in the understanding of the biology of restenosis indicate that intimal hyperplasia of smooth muscle cells is the predominant cause for restenosis. Therefore, therapeutic agents that inhibit vascular smooth muscle cell proliferation should be candidate drugs to prevent restenosis. Heparin has documented antiproliferative effects on smooth muscle cells, and the availability of low molecular weight heparins that lack anticoagulant properties makes them ideal agents. Glucocorticoids have wide effects on inflammatory and wound healing events and inhibit smooth muscle cell growth in culture and in animal models of arterial injury. Recent laboratory data suggest that combination therapy with both low molecular weight heparin and hydrocortisone may be a powerful treatment regimen to limit restenosis.
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PMID:Pharmacologic roles of heparin and glucocorticoids to prevent restenosis after coronary angioplasty. 201 69

Much of the research related to cardiopulmonary bypass in recent years has been directed toward defining the changes in plasma and blood cells during bypass. In this review, recent information is reexamined for six areas of current interest. These areas are complement activation, immune response, anaphylactic reactions, coagulation, and cerebral dysfunction. Complement may be activated by either the classical or alternate pathway during cardiopulmonary bypass and protamine administration. Membrane oxygenators appear to diminish the degree of complement activation. Complement is a major factor in the whole body inflammatory response; which often accompanies cardiopulmonary bypass. A product of complement activation, C5a- desArg, causes activation and aggregation of granulocytes. Other products of complement activation lead to lysis of blood cells including granulocytes and red cells. Bubble oxygenators appear to have a distinct disadvantage compared to membrane oxygenators regarding infection. Airborne microorganisms are more likely to be entrained into circulating blood with bubble oxygenators than with membrane oxygenators. Bubble oxygenators cause a greater decrease in leukocyte number and function than membrane oxygenators. Anaphylactic reactions have been associated with use of antibiotics, blood products, protamine, and volume expanders during cardiopulmonary bypass. Protamine reactions may be on an immunological basis or due to direct toxicity of the drug. Free radicals including superoxide, hydrogen peroxide, and the hydroxyl radical may be generated during cardiopulmonary bypass and reperfusion. Free radical scavengers including; vitamin E, coenzyme Q, vitamin C, mannitol, and glutathione have been studied. The avoidance of blood transfusion because of risk of transmitted infection including AIDS has become a major goal in cardiac surgery. Factors that correlate with increased transfusion requirement include low hematocrit, female gender, increased age, small body size, low ejection fraction, reoperation, and emergency operation. Heparin resistance due to antithrombin III deficiency is being recognized more commonly. Antithrombin III deficiency may be corrected with fresh frozen plasma. Patients with heparin induced thrombocytopenia may be difficult to manage. Several management protocols are suggested. The most straightforward appears to be the use of aspirin preoperatively and platelet transfusions postoperatively. The incidence of cerebral dysfunction after cardiopulmonary bypass depends on the sensitivity of the test or indicator used. Perioperative stroke is associated with intrinsic cerebrovascular disease and atherosclerosis of the ascending aorta. Retinal angiograms during cardiopulmonary bypass show that microemboli are very common. Cerebroplegia has been shown to extend the period of safe circulatory arrest in animals. Much of the new knowledge concerning cardiopulmonary bypass is the result of close collaboration between cardiac surgeons and nonsurgical scientists.
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PMID:Pathophysiology of cardiopulmonary bypass: current issues. 213 41

A sorbent based on heparin fraction with low affinity for antithrombin III is proposed for low density lipoproteins apheresis in hypercholesterolemia. Heparin was fractionated on antithrombin III-Sepharose; fractions with high and low affinity for antithrombin III were immobilized on CNBr-activated Sepharose 4B. Both sorbents appeared to have an LDL-binding capacity essentially similar to that of the sorbent based on unfractionated heparin. However only plasmasorption on a low affinity heparin-containing sorbent did not reduce plasma antithrombin III. Hence the use of this sorbent may be advantageous over the currently applied sorbents with unfractionated heparin in the treatment of familial hypercholesterolemia.
Atherosclerosis 1990 Sep
PMID:Apheresis of low density lipoproteins using a heparin-based sorbent with low antithrombin III binding capacity. 224 21

Angina presents itself to us as a continuous spectrum of ischemic syndromes. The disease is multifactorial, and within the same patient different pathophysiological mechanisms may occur at different times and in succession. Several factors may be causative at a particular moment of the disease process and the very next moment a different mechanism may prevail or spontaneous improvement may occur. Among these are stable atheroma with episodic increased vasomotor tone, fissured plaques with intraluminal and/or intraintimal thrombus, thrombocyte aggregation in greater than 70% intraluminal narrowing from ulcerated plaques, as well as frank spasm of vessels without major atherosclerosis. Consequently, there will never be one therapy for every case of (un)stable angina nor will there ever be a best therapy for all. Rather, a stepped approach appears the most likely to be successful. This begins with bed rest and requires vasodilator therapy with nitrates and/or Ca2+ antagonists and beta blockade. If this triple therapy does not "cool" the symptoms within 6-12 hours, semiurgent arteriography is indicated. Depending on the pathophysiology found, thrombolytic therapy with streptokinase or tissue plasminogen activator, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) must be carried out early. Heparin in the short term and aspirin in the long term protect best against late complications. The moment is now here when infarction or death after an attack of angina pectoris should be rare.
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PMID:Calcium antagonists for angina pectoris. 289 19

Restenosis after angioplasty is probably related to 2 processes: thrombosis and recurrence of atherosclerosis. Many approaches to altering these processes are available, but to date none has shown a high rate of success. Heparin has properties relevant to both processes; this makes it an attractive compound for further study. The anticoagulant action of heparin is well known. It is mediated primarily though complex formation with antithrombin III, which leads to a conformational change and an increased rate of thrombin inactivation. Heparin has additional antithrombotic actions, largely mediated through the formation of the same complex, but involving precursor elements such as factor Xa. These actions of heparin can be localized to different portions of the large, complex molecule. Additionally, experimental studies have demonstrated an antiproliferative action of heparin, a property that may be relevant to smooth muscle cell proliferation after angioplasty. This is mediated by a fairly small, functionally distinct nonanticoagulant portion of the heparin molecule. Fragments of heparin possessing particular actions are being investigated experimentally and clinically. Continued investigations of the structure and function of heparin promise to lead to a decreased rate of restenosis and a better understanding of the mechanisms of angioplasty.
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PMID:Anticoagulation and restenosis after percutaneous transluminal coronary angioplasty. 295 35

Familial hypercholesterolaemia is caused by genetic defects in the cellular metabolism of cholesterol (C) and is characterized by high levels of low-density lipoproteins (LDL) and premature atherosclerosis. The C is carried in the plasma mainly as an LDL-C complex, and removal of the latter from plasma is highly desirable. This task can be achieved by selective haemoperfusion (HP), thereby eliminating the need for plasmapheresis. Agarose beads (2 per cent agarose, 0.85 to 1.4 mm in diameter) were prepared, and crosslinked with epichlorohydrin. Heparin and/or ethanolamine were subsequently attached. The beads thus obtained were found to be suitable for the removal of LDL-C from the whole blood of hypercholesterolaemic rabbits, using a simple HP technique. A single two-hour HP treatment with a 40 ml column packed with active agarose beads resulted in a 30 per cent decrease in the C plasma level in the experimental animals. Our previous, in vitro, studies with the plasma of hypercholesterolaemic patients showed a high selectivity of the beads for LDL. Yet when used with hypercholesterolaemic rabbits, a relatively high amount of HDL was also removed from the blood. This can be attributed to a significant difference between the structure of human hypercholesterolaemic lipoproteins and that of rabbits. Upon treatment of blood using the active agarose beads, no abnormalities in plasma and blood composition were detected, except for some prolongation of PT. It is to be hoped that this new system will replace the presently used and highly expensive plasmapheresis.
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PMID:Cholesterol removal by haemoperfusion of whole blood in vivo. 356 Oct 33

Mast cell population was studied in rats with experimental atherosclerosis. It has been established that animals kept for 8 months on atherogenic diet revealed marked changes in mast cell population. Predominance of light cells and cell defects were noted. Heparin saturation index was reduced (0.35), as compared to the control (3.9). Stimulation of anticoagulation system by DIP-alpha-thrombin in such animals revealed no heparin in the blood. Mast cell subpopulation was characterized by light cell predominance and low heparin saturation index. The nature of cell degradation remained unchanged. The data obtained indicate the defects in mast cell pool in animals with experimental atherosclerosis.
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PMID:[Mast cell population in rats with experimental atherosclerosis]. 382 23

Heparin was fractionated on an affinity column of bovine milk lipoprotein lipase (LpL) immobilized to Affi-Gel-15. The bound heparin, designated high-reactive heparin (HRH), enhanced LpL activity, presumably by stabilizing the enzyme against denaturation. The unbound heparin fraction had no observable effect on the initial rate of enzyme activity. However, at longer times of incubation there was inhibition of LpL activity. LpL-specific HRH also showed a high, Ca2+-dependent precipitating activity towards human plasma low density lipoproteins (LDL). Since LpL and LDL both bind to heparin-like molecules at the surface of the arterial wall, we suggest that their similar heparin-binding specificity may have physiological consequences as it relates to the development of atherosclerosis.
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PMID:Heparin binding to lipoprotein lipase and low density lipoproteins. 404 7

Heparin-Sepharose affinity chromatography resolved rat lipoproteins isolated in the density range 1.019-1.063 g/ml into two distinct fractions. The first, which eluted with 150 mM NaCl, was shown by immunodiffusion and by polyacrylamide gel electrophoresis to contain predominantly apo E. On this basis the major lipoprotein present is identified as high density lipoprotein1 (HDL1). The second, eluted with 325 mM NaCl, contains predominantly apoprotein B by the same techniques. The main lipoprotein present is therefore identified as low density lipoprotein (LDL). The lipid composition of the two lipoproteins is similar. Both are rich in cholesterol ester, with a free to ester cholesterol ratio of about 1 to 2.5. From lipid and protein analyses on the two fractions, the plasma concentrations of HDL1 and LDL can be calculated to be about 14 and 12 mg/100 ml, respectively. Their mean diameters are 13 +/- 2 nm and 18 +/- 5 nm, respectively.
Atherosclerosis 1984 Nov
PMID:The use of heparin-sepharose affinity chromatography to separate two distinct lipoproteins from the low density lipoprotein fraction of rat plasma. 644 May 66


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