Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.
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PMID:Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells. 925 3

Recent studies in man and human apolipoprotein A-I transgenic animals emphasize the significance of apolipoprotein A-I and high density lipoprotein in antiatherogenesis. Several drugs and other compounds, e.g. phenobarbital, gemfibrozil, fenofibrate, prednisone, estrogen and alcohol, induce apolipoprotein A-I synthesis. They commonly produce serum lipoprotein patterns typical of a low risk of coronary heart disease, and many of them have been found to prevent atherogenesis, reduce coronary heart disease mortality and increase survival. These compounds act against atherosclerosis by using one or several mechanisms that include overexpression of the apolipoprotein A-I gene with an increase in serum apolipoprotein A-I and high density lipoprotein and promotion of reverse cholesterol transport, upregulation of the low density lipoprotein receptor gene with a decrease in serum apolipoprotein B and low density lipoprotein, maintenance of endothelial cell function and protection against thrombosis. They have been found to raise high density lipoprotein cholesterol and apolipoprotein A-I together with a decrease in cholesterol ester transfer protein activity, and to induce hepatic cholesterol 7 alpha-hydroxylase and cholesterol and bile acid elimination from the body. By raising the activities of apolipoprotein A-I/high density lipoprotein-associated paraoxonase and other antioxidative enzymes, the inducers have the capacity to prevent atherogenesis in arterial walls through inhibition of the oxidative modification of low density lipoprotein. Other antiatherogenic vascular actions of high density lipoprotein include interference with low density lipoprotein aggregation and uptake by endothelial cells, and competition with low density lipoprotein for endothelial-localized low density lipoprotein receptors. Apolipoprotein A-I/high density lipoprotein beneficially enhances fibrinolysis, decreases platelet aggregation, increases prostacyclin production and stabilization and prevents atherogenic immune and inflammatory responses. This gene activation or microsomal induction can prevent atherosclerosis and is a basis for tailoring effective new agents and optimal non-invasive therapy against atherosclerotic vascular disease to promote health and enhance longevity.
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PMID:Gene activation, apolipoprotein A-I/high density lipoprotein, atherosclerosis prevention and longevity. 929 1

There is no doubt about the positive influence of acetylsalicylic acid on vascular disease. The antithrombotic therapy with acetylsalicylic acid is a fundamental of secondary prevention of vascular events, especially in nonfatal myocardial infarction, instable angina pectoris, stroke and in patients with amaurosis fugax. Clinical studies done since 1990 about the effect of a low-dose therapy confirmed the experimental results, which showed that 25-50 mg acetylsalicylic acid per day are enough, to suppress platelet function as far as necessary, without influencing the protective function of prostacyclin synthesis. Side-effects can be reduced to a minimum with a reduced dosage. The wide-spread use of a low-dose acetylsalicylic acid therapy in primary prevention especially in patients at high risk has to be reevaluated in further studies.
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PMID:[Acetylsalicylic acid after myocardial infarct]. 934 Sep 19

The endothelium plays a crucial role in the regulation of vascular function through the release of locally important molecular effectors such as endothelium-derived relaxing factor (EDRF) and prostacyclin. Endothelial cells also regulate vascular patency and tissue perfusion by inhibiting platelet aggregation and thrombosis, suppressing intimal proliferation, and maintaining vascular tone. Disturbances of the regulatory functions of the endothelium contribute to the pathophysiology of various disease states, including cardiovascular disease and stroke. Most studies focused on endothelial control of vasomotion and, in particular, on the action of EDRF; many studies have also emphasised that altered endothelial control of fibrinolysis and intimal growth influence the clinical expression of atherothrombotic disease. Importantly, understanding the pathophysiological role of endothelial dysfunction may lead to new therapeutic approaches for disease states caused by vascular disease.
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PMID:Endothelial dysfunction and atherothrombotic occlusive disease. 936 Aug 51

Abnormal biosynthesis of thromboxane and prostacyclin has been implicated in patients with primary pulmonary hypertension and secondary pulmonary hypertension associated with congenital heart disease, and could be involved in the pathogenesis of pulmonary vascular disease. The chronic effects of an oral prostacyclin analogue, beraprost sodium, on thromboxane and prostacyclin biosynthesis and on pulmonary circulation were investigated in 15 children with pulmonary hypertension. The plasma concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured, as was the urinary excretion of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, which are stable metabolites of thromboxane A2 and prostacyclin, respectively. In patients with pulmonary hypertension, the plasma concentration of thromboxane B2 and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were greater than in healthy controls: 210 +/- 49 versus 28 +/- 4 pg/mL (P < 0.05) and 32.6 +/- 8.9 versus 5.7 +/- 1.8 (P < 0.01), respectively. After 3 months of administration of beraprost, the plasma concentration of thromboxane B2 and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were reduced significantly: 210 +/- 49 to 98 +/- 26 pg/mL (P < 0.01) and 32.6 +/- 8.9 to 18.0 +/- 6.7 (P < 0.05), respectively. In contrast, the plasma concentrations of 6-keto-prostaglandin F1 alpha in patients were slightly but not significantly higher than in controls, and did not change significantly after administration of beraprost. The concentrations of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha in urine correlated significantly with thromboxane B2 and 6-keto-prostaglandin F1 alpha, respectively, in plasma. Beraprost improved the imbalance of thromboxane and prostacyclin biosynthesis and has a potential efficacy for preventing the progressive development of pathological changes in pulmonary vasculature.
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PMID:Chronic effects of oral prostacyclin analogue on thromboxane A2 and prostacyclin metabolites in pulmonary hypertension. 958 94

Although lung transplantation is considered a definitive treatment of patients with advanced pulmonary vascular disease and pulmonary hypertension, advances in the success of the medical management of patients with pulmonary hypertension make it less clear as to when to refer a patient for transplantation. Coumadin anticoagulation is associated with improved survival in all patients, and calcium channel blockers therapy with improved survival in very select patients. Chronic prostacyclin represents a newer therapy that seems to have a dramatic impact on patients' functional class and survival. As improvements continue in the medical management in pulmonary hypertension, and in survival of patients undergoing lung transplantation, the guidelines for patient selection should be constantly evolving.
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PMID:Lung transplantation for pulmonary hypertension: patient selection and maintenance therapy while awaiting transplantation. 962 Apr 61

The role of interferon (IFN) in the treatment of chronic myeloid leukaemia (CML) has been established. Many adverse effects have been reported, but vasospasm has been extremely rare. We report 2 CML patients who developed such complications. A 56-year-old female had been on IFN for 3 years with haematological and cytogenetic remission, when she developed an anginal syndrome followed by acute ischaemia. Coronary catheterization revealed normal arteries. After discontinuation of IFN her cardiac complaints disappeared and she needed no medication. A 61-year-old patient had been on IFN for 1 year when he presented with Raynaud's phenomenon. No evidence of collagen vascular disease could be documented. IFN discontinuation and intravenous administration of iloprost (a prostacyclin analogue) resulted in the disappearance of the vascular complications. IFN appears to have a beneficial effect on the course and prognosis of CML. However, we have to be aware of the potential complications and adverse effects which can be related to IFN. Neither our experience nor the literature provides convincing recommendations regarding the management of such patients. We suggest proceeding with IFN at lower doses, especially in those who have achieved a cytogenetic response, as our first patient.
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PMID:Interferon-induced vasospasm in chronic myeloid leukaemia. 979 41

Endothelial cells control the tone of the underlying vascular smooth muscle by secreting vasodilator substances (prostacyclin, nitric oxide and endothelium-derived hyperpolarizing factor). These vasodilator substances also contribute to the antithrombogenicity of the normal endothelium, and inhibit cellular growth. In coronary vascular disease, the ability of the endothelium to secrete vasodilator substances is reduced, while the propensity to release endothelium-derived contracting factors is increased. In particular, the reduced release of nitric oxide in response to aggregating platelets, thrombin and circulating catecholamines favours the occurrence of thrombosis and vasospasm, and plays a key role in the initiation of the atherosclerotic process. From the therapeutic point of view, the best available way to enhance the release of endothelium-derived nitric oxide and hyperpolarizing factor is to inhibit converting enzyme. This will protect endogenous bradykinin from breakdown and prolong its action on endothelial receptors.
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PMID:Endothelial dysfunction and inhibition of converting enzyme. 979 35

1. Nitric oxide (NO) has important roles in physiological vasodilatation, cytotoxicity and vascular disease. Nitric oxide and prostacyclin (PGI2), both released from the endothelium, act synergistically to inhibit platelet aggregation and adhesion. These autacoids also inhibit the adhesion and migration of leucocytes and, in some arteries, they synergize in terms of vasodilation. 2. The development of atherosclerosis and hyperlipaemia per se is accompanied by impairment of endothelium-dependent vasodilation. 3. Atherosclerosis is associated with marked changes in the activity of isoforms of NO synthase (NOS) in the artery wall, including increased expression of the NOS2 (inducible) isoform in complex human lesions as well as in the neointima of experimental animal models. 4. Failure of NO release from the endothelium with normal physiological stimuli, which has been attributed to a defect in the operation of the endothelial NOS (NOS3), provides conditions propitious for leucocyte adhesion, vasospasm, thrombosis and, in addition, may promote increased proliferation of intimal cells. 5. Nitric oxide and superoxide anions generated by inflammatory cells in atherosclerosis react to form cytodestructive peroxynitrite radicals, potentially causing injury to the endothelium and myocytes, and this may be a factor in apoptosis of cells leading to plaque rupture. 6. We have been able to reverse these NO defects with therapeutic agents, including angiotensin-converting enzyme inhibitors, antagonists of platelet-activating factor and NO donor compounds, all offering promise in protecting against some manifestations of vascular disease.
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PMID:Nitric oxide in atherosclerosis: vascular protector or villain? 980 90

This review recounts recent advances in the understanding and treatment of the processes that cause pulmonary hypertension in infancy and childhood. New discoveries have begun to unveil connections between the basic physiological mechanisms responsible for the regulation of pulmonary vascular tone and the abnormal responses of the pulmonary vasculature in a variety of disease conditions. These discoveries raise hope for new therapeutic interventions that may improve the high mortality and morbidity of both children and adults with pulmonary vascular disease. In the meantime, treatment efforts continue to be focused on the relief of pulmonary vasoconstriction with inhaled nitric oxide and intravenous prostacyclin in the short term and oral calcium channel blockers as the mainstay of long-term therapy. Lung transplantation often remains as the only viable option for continued survival when the pulmonary vascular disease is progressive.
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PMID:Long-term therapy for pulmonary hypertension in children. 1034 99


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