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

In the United States, congestive heart failure (CHF) was the underlying cause of death for approximately 38,000 persons in 1990; of those deaths, approximately 92% were among persons aged > or = 65 years. CHF, a clinical syndrome defined as a chronic inadequate contraction of the heart muscle resulting in insufficient cardiac output, is a manifestation of one or more underlying conditions, including systemic or pulmonary hypertension or a history of other heart diseases (e.g., myocardial infarction, atherosclerosis, cardiomyopathy, congenital heart disease, or rheumatic fever). The long-term prognosis of CHF depends on the underlying condition and the response of that condition to treatment. Despite declines in death rates for ischemic heart disease and cerebrovascular disease, improvements in detection and treatment of hypertension, and considerable advances in the diagnosis and management of CHF, mortality from CHF has increased since 1980. This report summarizes trends in CHF mortality in the United States during 1980-1990 and presents state-specific mortality data for 1990 (the most recent year for which such data are available).
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PMID:Mortality from congestive heart failure--United States, 1980-1990. 829 29

In recent years, two key concepts having numerous interrelationships were advanced for the understanding of various cardiovascular diseases: the "endothelial dysfunction" and the "arterial remodelling". Both endothelial dysfunction and arterial remodelling occur in various pathologies including essential hypertension, heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extra-cellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extra-cellular matrix.
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PMID:The arterial wall: a new pharmacological and therapeutic target. 883 98

The development of atherosclerosis is clearly linked to the level of blood pressure. This is illustrated by the difference of atheroma formation in arteries as compared to veins, the development of atherosclerosis in veins transplanted to the arterial circulation or the finding of atherosclerosis also in the pulmonary circulation as an effect of pulmonary hypertension. Several experimental studies have also illuminated the strong link between high blood pressure and the development of atherosclerosis. From a therapeutic point of view it is worth noting that the lowering of blood pressure per se has a positive effect on the development of atherosclerosis. In particular, calcium antagonists have been shown, in numerous experimental studies, to have an antiatherosclerotic effect. The positive results in animal studies led to studies in man, the first of which was the MIDAS Study. The Multicentre Isradipine Diuretic Atherosclerosis (MIDAS) Study was a comparison between the dihydropyridine-derived calcium antagonist isradipine and hydrochlorothiazide in 883 hypertensive patients. B-mode ultrasonography of the carotid artery was used in order to evaluate changes in wall thickness and the development of atherosclerotic plaques during a 3-year period. The final publication has yet to appear in a medical journal. However, the study and its main findings have been presented at several international scientific meetings. In brief, isradipine was significantly more effective than hydrochlorothiazide in preventing an increase in intima-media thickness at several points of measurement in the carotid artery in spite of the fact that systolic blood pressure was not lowered as effectively by isradipine as by the diuretic therapy. There are numerous lessons to be learnt from MIDAS for future studies of this kind. A good example of this is the European Lacidipine Study of Atherosclerosis (ELSA) which is currently in progress in several European countries. By careful analysis of MIDAS an improved study design has been created, which should result in a definitive and irrefutable answer to the issue of the clinical importance of calcium antagonist treatment in the prevention of atherosclerosis.
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PMID:How to study the role of hypertension in atherosclerosis. Lessons from MIDAS. Multicentre Isradipine Diuretic Atherosclerosis Study. 897 77

One hundred and fifty-four (5.7%) of 2690 patients who had been admitted to a hospital for sarcoidosis of intrathoracic lymph nodes (ITLN) were diagnosed as having various cardiovascular diseases (hypertensive disease, congestive lung, congenital and acquired cardiac diseases, atherosclerosis, aortic aneurysms and myocarditis). Misinterpretation of the X-ray film of the lung root, no lateral X-ray films, inadequate scope of objective studies of the cardiovascular system are the most common errors at prehospital examination. The obligatory making of lateral X-ray films, tomograms, the use of computed tomography, ECG and phonocardiography, and thorough account of objective data are valuable additional methods in the differential diagnosis of ITLN sarcoidosis and cardiovascular diseases accompanied by the appearance of wide truncal large vessels of the root due to pulmonary hypertension.
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PMID:[The differential diagnostic characteristics of sarcoidosis of the intrathoracic lymph nodes and of cardiovascular diseases]. 902 96

Hypoxia has profound effects on blood vessel tone. Acute hypoxia causes pulmonary vasoconstriction and chronic hypoxia causes smooth muscle cell replication and extracellular matrix accumulation resulting in vessel wall remodeling. The cellular responses to hypoxia involve complex cell-cell interactions mediated by the release of growth factors, cytokines and biological messengers. We have reported that hypoxia increases the expression of a number of genes encoding vascular cell mitogens produced by endothelial cells: platelet-derived growth factor B (PDGF-B); endothelin-1 (ET-1); and vascular endothelial growth factor (VEGF). A 28-bp enhancer in the 5' upstream region of the VEGF gene mediates the expression of VEGF by endothelial cells under conditions of hypoxia. Hypoxia, however, has opposite effects on the vasodilator nitric oxide (NO); hypoxia suppresses both the transcriptional rate of the endothelial nitric oxide synthase gene and the stability of its mRNA. These endothelial-dependent processes would lead to vessel wall remodeling characteristic of a number of diseases from atherosclerosis to pulmonary hypertension. The smooth muscle cell also responds to hypoxia. It increases the transcriptional rate of the heme oxygenase gene-1 responsible for the breakdown of heme to carbon monoxide (CO) and biliverdin. CO is a vasodilator with properties similar to the well-studied molecule NO. CO suppresses the production of ET-1 and PDGF-B by endothelial cells. The regulated production of NO and CO under hypoxia, therefore, results in complex feedback loop interactions leading to altered smooth muscle cell growth in an autocrine and paracrine manner.
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PMID:Mechanisms by which oxygen regulates gene expression and cell-cell interaction in the vasculature. 902 18

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease resulting from the thromboembolic obstruction of the segmental and/or large size pulmonary arteries, subsequently leading to pulmonary arterial hypertension. Incomplete resolution of acute pulmonary emboli and thrombus organization are believed to be important for the development of the disease. Primary pulmonary hypertension (PPH) is a further disease that at present is poorly understood but shows a clinical picture similar to CTEPH. Since lipoprotein(a) [Lp(a)]. a genetically determined risk factor for atherosclerosis and thrombosis, has been found increased in plasma of patients with deep vein thrombosis and pulmonary embolism, we measured plasma Lp(a) levels in 40 patients with CTEPH and 50 patients with PPH and compared them to 50 matched controls. The median for Lp(a) plasma levels was significantly higher in CTEPH patients (26.6 mg/dl) than in PPH patients (9.6 mg/dl) and controls (7.2 mg/dl). Increased plasma Lp(a) could, therefore. play a significant role in the mechanisms of ongoing thrombosis and thrombus organization in CTEPH, while its possible role in PPH can be limited to a small number of patients.
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PMID:Plasma Lp(a) levels are increased in patients with chronic thromboembolic pulmonary hypertension. 971 43

Endothelin-1 (ET-1) is the most potent vasoconstrictor yet described. The active 21-amino-acid peptide is derived from the conversion of the inactive precursor "Big ET-1" by an enzyme called endothelin-converting enzyme. In addition to its potent action as a vasoconstrictor, endothelin promotes growth and proliferation of smooth muscle and myocardial hypertrophy. ET-1 levels are elevated in acute myocardial infarction (MI), atherosclerosis, renal failure, diabetes, pulmonary hypertension, and congestive heart failure (CHF). ET-1 levels correlate extremely well with the seriousness of the pathophysiologic condition. ET-1 levels at 72 h post MI accurately predict long-term survival. In patients with heart failure, ET-1 levels also predict long-term outcome, with the prognosis being severely compromised in patients with elevated ET-1 levels. Levels of plasma big ET-1 have been demonstrated to predict 1-year mortality and have been shown to be a better predictor of 1-year outcome than plasma atrial natriuretic peptide and norepinephrine, NYHA class, age, and echocardiographic left ventricular parameters. Although a small number of studies have reported beneficial effects of ACE inhibitors on ET-1 levels in animal models, most reports in humans have not found an effect of ACE inhibitors on ET-1 levels. Only one ACE inhibitor, fosinopril, has been shown to be effective in normalizing ET-1 levels in clinically relevant situations, such as the long-term study of patients with CHF. This observation may point to a superior role of fosinopril compared with other ACE inhibitors in CHF patients and may indicate beneficial effects of fosinopril beyond blood pressure control.
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PMID:Neurohormonal markers of clinical outcome in cardiovascular disease: is endothelin the best one? 973 39

1. Changes in the environmental oxygen tension to which cells are exposed in vivo result in physiological and sometimes pathological consequences that are associated with differential expression of specific genes. 2. Low oxygen tension (hypoxia) affects endothelial cellular physiology in vivo and in vitro in a number of ways, including the transcriptionally regulated expression of vasoactive substances and matrix proteins involved in modulating vascular tone or remodelling the vasculature and surrounding tissue. 3. Hypoxia results in the transcriptional induction of genes encoding vasoconstrictors and smooth muscle mitogens (PDGF-B, endothelin-1, VEGF, thrombospondin-1) and genes encoding matrix or remodelling molecules (collagenase IV (MMP-9), thrombospondin-1) and reciprocal transcriptional inhibition of vasodilatory or anti-mitogenic effectors (eNOS). 4. Oxygen appears to signal through a novel haem-containing sensor and signals initiated by this sensor alter the levels and DNA-binding activity of transcription factors such as activating protein (AP)-1, nuclear factor-kappa B and hypoxia-inducible transcription factor-1. 5. The genes encoding vasoactive factors regulated by oxygen tension are themselves also regulated by the vasoactive agent nitric oxide (NO). 6. Nitric oxide and oxygen transduce similar signals (i.e. their absence results in identical patterns of gene expression in endothelial cells and other cell types). 7. Thus, NO can feedback on and modulate signals induced by hypoxia and vice versa. For example, NO, which can act directly on smooth muscle cells as a vasodilator, can also facilitate vasodilation indirectly by reversing the production of vasoconstrictors induced by hypoxia. 8. Short-term exposure of endothelial cells to low oxygen tension results in the elaboration of predominantly vasoconstricting effectors, while longer-term and more severe hypoxic exposure generates factors that can induce smooth muscle proliferation and remodelling. 9. Thus, the endothelial cell response to hypoxic stress can result in two different consequences in the surrounding tissues, depending on the duration of the exposure: short-term exposure causes physiological and reversible modulation of vascular tone and blood flow; chronic hypoxic stress results in irreversible remodelling of the vasculature and surrounding tissues, with smooth muscle proliferation and fibrosis. 10. This dichotomy of responses to hypoxia may explain, in part, both the acute and chronic pathophysiological sequelae of diseases characterized by regional hypoxia, including atherosclerosis, pulmonary hypertension, sickle cell disease and systemic sclerosis (scleroderma).
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PMID:Endothelial cell responses to hypoxic stress. 1090 94

Antiphospholipid Syndrome (APS) was first described by Hughes and sometimes called as Hughes syndrome. Recent studies revealed that the antigen to anticardiolipin antibody (aCL) is not cardiolipin itself but co-factor beta 2-GPI which expresses its epitope when it combines cardiolipin or gets oxidized. Lupus Anticoagulant is now possibly considered as anti-prothrombin antibody. Livedo including Snedden syndrome, pulmonary hypertension and skin ulcer became considered as the part of symptoms of this disease. In ISAPA 1998, it is reported from several laboratories that IgA aCL is also pathogenic to thrombosis as well as IgG aCL. Atherosclerosis is also accelerated by aCL. Catastrophic APS is rare but fatal, reported 3 cases in Japan and 50 cases in the world.
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PMID:[Antiphospholipid syndrome]. 1007 9

In 1980, Furchgott and Zawadzki demonstrated that the relaxation of vascular smooth muscle cells in response to acetylcholine is dependent on the anatomical integrity of the endothelium. Endothelium-derived relaxing factor was identified 7 years later as the free radical gas nitric oxide (NO). In endothelium, the amino acid L-arginine is converted to L-citrulline and NO by one of the three NO synthases, the endothelial isoform (eNOS). Shear stress and cell proliferation appear to be, quantitatively, the two major regulatory factors of eNOS gene expression. However, eNOS seems to be mainly regulated by modulation of its activity. Stimulation of specific receptors to various agonists (e.g., bradykinin, serotonin, adenosine, ADP/ATP, histamine, thrombin) increases eNOS enzymatic activity at least in part through an increase in intracellular free Ca2+. However, the mechanical stimulus shear stress appears again to be the major stimulus of eNOS activity, although the precise mechanisms activating the enzyme remain to be elucidated. Phosphorylation and subcellular translocation (from plasmalemmal caveolae to the cytoskeleton or cytosol) are probably involved in these regulations. Although eNOS plays a major vasodilatory role in the control of vasomotion, it has not so far been demonstrated that a defect in endothelial NO production could be responsible for high blood pressure in humans. In contrast, a defect in endothelium-dependent vasodilation is known to be promoted by several risk factors (e.g., smoking, diabetes, hypercholesterolemia) and is also the consequence of atheroma (fatty streak infiltration of the neointima). Several mechanisms probably contribute to this decrease in NO bioavailability. Finally, a defect in NO generation contributes to the pathophysiology of pulmonary hypertension. Elucidation of the mechanisms of eNOS enzyme activity and NO bioavailability will contribute to our understanding the physiology of vasomotion and the pathophysiology of endothelial dysfunction, and could provide insights for new therapies, particularly in hypertension and atherosclerosis.
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PMID:Endothelium-derived nitric oxide and vascular physiology and pathology. 1044 89


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