Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The degradation of elastin during various pathological processes such as emphysema or arteriosclerosis was demonstrated by several investigators. In the present work, we adapted an ELISA technique for the determination of elastin peptide (EP) levels in human sera and plasma, in healthy and arteriosclerotic subjects. This test makes use of human aorta elastin hydrolyzed by a chemical procedure (kappa-elastin) instead of EP produced by pancreatic or leukocyte elastase. Polyclonal antibodies to this antigen were obtained in rabbits. The indirect ELISA procedure is sensitive, specific and reproducible. No correlation could be demonstrated between EP level and anti-EP antibody concentration of IgG or IgM types determined in the same serum samples. These antibodies did not interfere with EP determinations. EP concentration did not change with age in control subjects. In obliterative arteriosclerosis of the legs and in type IIb hyperlipoproteinemia, EP levels showed a marked increase, while in hypertension, ischemic heart disease and diabetes mellitus, the increase was moderate. In stroke, only slight changes were observed. In type IV hyperlipoproteinemia, EP levels were lower than in controls.
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PMID:Determination of elastin peptides in normal and arteriosclerotic human sera by ELISA. 213 61

Although indapamide has been used for many years as a first-line treatment of hypertension, it is only recently that some of its activities on the changes of the cardiovascular system, brought on by age and high blood pressure, have been studied. Indapamide appears to reduce blood pressure by a combined diuretic and direct vascular activity reducing vascular reactivity and total peripheral resistance. In addition, it has discrete effects on a number of interrelated systems that may protect the cardiovascular system. Indapamide reduces intracellular calcium levels, maintains magnesium ions, but reduces phosphate ions that may be involved in arterial rigidity. Circulating catecholamines remain unchanged but there is a reduction in normetanephrine, suggesting a reduction in sympathetic tone. It stimulates prostacyclin synthesis, increases levels of circulating prostacyclin, reduces platelet aggregation and stimulates the vasodilation elicited by endothelium-derived relaxing factor in the presence of bradykinin. In addition, it inhibits the formation of the vasoconstrictor prostanoid, thromboxane A2. The free radical scavenging activity of indapamide could also protect the vascular smooth muscle from the reperfusion injury of cerebral and myocardial ischemia. Indapamide induces a reduction in cerebral ischemia after carotid ligation. Unlike some other antihypertensives, it does not upset the high-density/low-density lipoprotein-cholesterol balance, reducing the possible risk of atherosclerosis. Moreover, the combination of binding to elastin and reduction in uptake of calcium and phosphate into the smooth muscle could be a mechanism for reducing arterial rigidity seen in the elderly and hypertensive patient. In hypertensive patients, these properties induce an improvement in arterial compliance, and in the long term a reduction in left ventricular hypertrophy. These pharmacologic and clinical results, together with a good antihypertensive efficacy and acceptability, suggest that indapamide may be a preferential agent in the long-term cardiovascular protection of the hypertensive patient.
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PMID:Cardiovascular protective properties of indapamide. 218 50

We adapted a highly sensitive and reproducible ELISA technique for the determination of anti-elastin peptide antibodies of IgG type AEAb-IgG) and IgM type AEAb-IgM) in human sera. The determination was performed in the sera of 265 normal and diseased persons. The pathologies studied included obliterative arteriosclerosis of the legs, ischemic heart disease, stroke, diabetes mellitus, type IIb and IV hyperlipoproteinemia and hypertension. No clearcut correlation could be found between AEAb and age. In contrast, in arteriosclerotic patients and especially in obliterative arteriosclerosis of the legs and ischemic heart disease, the concentration of AEAb-IgG was significantly increased. The AEAb-IgM showed no change in the studied diseases. Both types of AEAb were decreased in type IV hyperlipoproteinemia. Anti-elastin antibodies may be involved in the pathomechanisms of the above diseases and the determination of antibody concentrations may be of some help in obliterative arteriosclerotic diseases.
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PMID:Determination of anti-elastin peptide antibodies in normal and arteriosclerotic human sera by ELISA. 264 31

In order to further investigate the role of the immune system in the arteriosclerotic process, we investigated the anti-elastin peptide antibodies (AEAb) of the IgG and IgM types by DOT immunobinding assay in the sera of patients suffering from various arteriosclerotic diseases. In total 232 control and pathological sera were studied. In obliterative arteriosclerosis of the legs 90%, ischemic heart disease 67% and hypertension 60% of sera were positive for AEAb of the IgG type independent of age. In the case of diabetes mellitus, however, the duration of the disease was determinant. In rheumatoid arthritis, the results were negative. No clear-cut positivity could be demonstrated in stroke patients either. These results indicate that AEAb can be detected in some diseases and DOT appears to be an appropriate method for the AEAb screening in various diseases.
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PMID:Immunology of elastin: study of anti-elastin peptide antibodies by DOT immunobinding assay. 331 75

Scanning electron microscopy and transmission electron microscopy were used together with tannic acid and ruthenium-red staining to examine connective tissue damage caused by acute myocardial ischemia for 20, 40 and 120 min in pig hearts. The microsphere blood flow technique revealed that blood flow was approximately 0.02 ml/min/g in inner, middle and outer thirds of the ischemic zone. After 20 min of occlusion of the left anterior descending coronary artery, the collagen network and microfilaments became irregularly arranged. After 40 min of occlusion, ruthenium-red positive glycoprotein material around the collagen fibrils and elastin began to disappear. After 2 h occlusion, the collagen fibrils and microfilaments had separated from the basement membrane. Collagen fibrils, elastic fibers, and microfilaments were broken down and were found in decreased quantities. These results have revealed that the connective tissue remains intact during the first 20 min of coronary occlusion despite zero blood flow and mild cellular changes but does undergo prominent alterations after 40 min of occlusion.
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PMID:Connective tissue changes in early ischemia of porcine myocardium: an ultrastructural study. 687 83

Although the nutritional essentiality of copper was established in 1928, a preoccupation with hematology delayed the discovery of cardiovascular disease from copper deficiency for more than a decade. Anatomical studies of several species of deficient animals revealed, interalia, aortic fissures and rupture, arterial foam cells and smooth muscle migration, cardiac enlargement and rupture, coronary artery thrombosis and myocardial infarction. Abnormal biochemistry in deficiency probably contributes to these lesions, e.g., decreased activities of lysyl oxidase and superoxide dismutase which result in failure of collagen and elastin crosslinking and impaired defense against free radicals. Copper deficiency also decreases copper in hearts and other organs and cells and increases cholesterol in plasma. Abnormal physiology from deficiency includes abnormal electrocardiograms, glucose intolerance and hypertension. People with ischemic heart disease have decreased cardiac and leucocyte copper and decreased activities of some copper-dependent enzymes. Copper depletion experiments with men and women have revealed abnormalities of lipid metabolism, blood pressure control, and electrocardiograms plus impaired glucose tolerance. The Western diet often is as low in copper as that proved insufficient for these people. Knowledge of nutritional history can be useful in addressing contemporary nutritional problems.
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PMID:Cardiovascular disease from copper deficiency--a history. 1072 36

Calcium antagonists effective in lowering blood pressure are a heterogeneous group including three main classes: phenylalkylamines, benzothiazepines and dihydropyridines. Dihydropyridines have a dual mode of action upon the endothelium contributing to their beneficial antihypertensive effects: (1) direct relaxation by inhibition of smooth muscle L-type calcium current, and (2) indirect relaxation through release of nitric oxide from the vascular endothelium. Calcium antagonists may affect many calcium-dependent events in the formation of atherosclerosis such as the localized accumulation of collagen, elastin, and calcium together with monocyte infiltration and smooth muscle proliferation and migration. In the INSIGHT calcification study, the overall treatment effect of nifedipine demonstrated significant inhibition of coronary calcium progression over a three-year period. Calcium antagonists improve symptoms and reduce ischemia in hypertensive patients with ischemic heart disease. Although in placebo-controlled trials calcium antagonists demonstrated a significant reduction in cardiovascular morbidity and mortality, they may be less effective than other types of antihypertensive drugs in preventing ischemic heart disease.
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PMID:Coronary benefits of calcium antagonist therapy for patients with hypertension. 1170 4

Four classes of agents capable of producing human illness have been identified: toxicity, heredity, infection and deficiency. The leading paradigm for the etiology and pathophysiology of ischemic heart disease in the 20th century was that of intoxication by too much of the wrong kind of dietary fat. This overemphasis on lipid metabolism persists because important data are neglected and because of inattention to details. For example, heart disease risk does not correlate with fat intake within nations in contrast to between nations. Also development of ischemic heart disease involves inter alia arterial spasm, cardiac rhythm, metabolism of connective tissue, glucose and homocysteine, plus paraoxonase activity and thrombus formation which generally are unaffected by dietary fat. Homocysteine thiolactone accumulates when homocysteine is high. This lactone specifically inhibits lysyl oxidase which depends on copper to catalyze cross linking of collagen and elastin in arteries and bone. The lactone is hydrolyzed by paraoxonase, activity of which can be decreased by copper deficiency. Just as cholesterol was an important focus for heart disease as intoxication, homocysteine can become an excellent focus for a paradigm shift to heart disease as deficiency because supplementation with several nutrients can alter homocysteine metabolism and decrease its plasma concentration. These supplements include betaine, copper, folate, pyridoxine and vitamin B-12. Opportunities for research on ischemic heart disease as deficiency disease are plentiful.
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PMID:Ischemic heart disease as deficiency disease. 1570 51

There are significant associations between moderate increases in serum homocysteine and three cardiovascular diseases: ischemic heart disease, deep vein thrombosis and pulmonary embolism, and stroke. An association between the presence of abdominal aortic aneurysm and elevated homocysteine plasma levels has been indicated. Although chronic systemic hypertension is the most common factor predisposing the aorta to dissection, homocysteinemia has never been known as the risk for aortic dissection except for that with Marfan syndrome. Homocysteinemia is suggested to be the risk for aortic dissection in Marfan syndrome and spontaneous cervical artery dissection. Reduced fibrillin-1 deposition into the extracellular matrix is found not only in Marfan syndrome but also in isolated ascending aortic aneurysm and dissection. The reduced matrix deposition produces a mild form of weakness of elastic tissue, which predisposes to ascending aortic aneurysm and dissection in patients who do not have the Marfan syndrome. The defect in fibrillin-1 leads to: (1) formation of elastin that is abnormally aggregated and more easily degraded by matrix metalloproteinases than is normal elastin; (2) upregulation of the synthesis of matrix metalloproteinases; (3) progressive destruction of connective tissue by these enzymes; (4) development of thoracic aortic aneurysms. Homocysteine causes premature breakdown in the arterial elastic fibers by activation of the elastolytic activities. Irreversible homocysteinylation of long-lived proteins should lead to cumulative damage and progressive clinical manifestations, and fibrillin-1 is seen as the paradigm of extracellular connective tissue proteins that are specially susceptible to homocysteine (and presumably homocysteine thiolactone) attack. The authors hereupon propose a novel hypothesis that homocysteine plays an important role in development of aortic dissection and that homocysteinemia is one of the risk factors for aortic dissection.
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PMID:Homocysteinemia is a risk factor for aortic dissection. 1578 May 1

Four classes of agents capable of producing human illness have been identified: toxicity, heredity, infection and deficiency. Examples of how members of these classes of etiologic agents can cooperate to produce illness were shown. The copper deficiency theory of ischemic heart disease and the homocysteine theory of arteriosclerosis were examined using concepts about cooperation. The Western diet so closely associated with these illnesses often is low in copper. Copper deficiency decreases the activity of methionine synthase which contributes to elevation of homocysteine, and of paraoxonase which impairs hydrolysis of homocysteine thiolactone, an inhibitor of lysyl oxidase. This copper-dependent enzyme initiates the cross-linking of collagen and elastin in arteries and bone. High homocysteine also impairs superoxide dismutase, a copper-dependent enzyme important in oxidative defense. Some genes affecting paraoxonase activity may respond to dietary copper. The copper deficiency theory of ischemic heart disease and the homocysteine theory of arteriosclerosis are inextricably entwined.
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PMID:How dietary deficiency, genes and a toxin can cooperate to produce arteriosclerosis and ischemic heart disease. 1754


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