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)

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

At has been reported that transplantation of appropriate cells, growth factors, and/or extracellular matrix may help the regeneration of damaged tissues or organs. Some growth factors, such as basic fibroblast growth factor(bFGF), have been successfully transferred to patients with ischemic heart disease. Embryonic dopamine neurons were also transplanted into the brains of patients with Parkinson's disease successfully. We have also performed cultured auto iris pigment epithelial cell (IPE) transplantation into the subretinal space after removal of choroidal neovascularization in patients with age-related macular degeneration (AMD). Here, we report the results of auto IPE transplantation in 35 patients, who could be followed for more than 6 months. We also tried to apply cell transplantation to other retinal diseases by managing the transplanted cells as introduced growth factor genes. Auto IPE transplantation was performed after removal of choroidal neovascular membranes (CNV). Visual acuity wes improved by more than 0.2 log MAR in 18 of 35 patients (51.5%), it was unchanged in 11 patients (31.5%), and it was worsened in 6 patients (17%). No significant difference was observed in comparison to patients who underwent CNV removal only. However, unlike the previous reports, we found no patients showing rejection. We also found that the cultured transplanted cells never showed proliferation under the retina or in the vitreous cavity and concluded that cultured auto IPE transplantation can be performed safely without complications. Next, we examined whether cell transplantation can be expanded to other degenerative retinal diseases. One of our results showed that host RPE may play an important role against the transplanted cells in the subretinal regions. When we introduced bFGF gene into the cells, we found synexpression cluster of the genes in the cells. One of the most prominent movements among the genes was lysyl oxidase like-1 gene, which plays an important role in the maturation of the extracellular collagen and in cell attachment. However, when we examined the cell attachment on the culture plates after 12 hours of culture, no significant difference was observed between the cells with or without bFGF. Further, when we examined the area of the cells transplanted into the subretinal space of rats during successive follow-up using fluorescein marker (EGFP), no statistical significance was observed. The gene expression pattern may be different when we introduce different growth factor gene. No antibody production was generated against the growth factor gene introduced cells after cell transplantation. Further, when we made transgenic mice expressing bFGF or Axokine cDNA in the RPE of rd mice, no photoreceptor degeneration was observed. One of the reasons was suspected to be that bFGF was expressed systemically by the promoter of tyrosinase related-protein 1 gene and may lead to lethality. Another reason was suspected to be suppression of the function of Axokine by the down-regulation of the ciliary neurotrophic factor or its receptor gene. Conversely, when we produced photoreceptor degeneration by constant light damage in the rats, we found partial photoreceptor rescue by transplantation of the growth factor gene introduced RPE. We show here the possibility that growth factor gene introduced cell transplantation may be applied to retinal diseases, if we select appropriate cells and genes.
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PMID:[Regeneration of the retina using pigment epithelial cell transplantation]. 1261 Aug 37

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

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

Myocardial ischemia leads to a decrease in copper (Cu) concentrations, along with collagen deposition in which Cu-dependent lysyl oxidase (LOX) catalyzes the cross-linking of collagens leading to tissue stiffness. The present study was undertaken to determine the relationship between decreased Cu concentrations and LOX activities in ischemic hearts of monkeys. Rhesus monkeys were subjected to coronary artery ligation, leading to ischemic infarction. At 8 weeks after the surgery, Cu concentrations and Cu-dependent cytochrome c oxidase (CCO) activities in the infarct area were significantly decreased. Unexpectedly, the Cu-dependent LOX activities in the same area were significantly increased. LOX proteins were accumulated in the cytosol of myofibroblasts, endothelial cells, and residual cardiomyocytes in the infarct area. In contrast, LOX was only found in fibroblasts and myocardial intercalated discs between cardiomyocytes in sham-operated controls. The LOX mRNA level was also increased in the infarct area compared to the sham operated control. This upregulation of LOX was associated with significant increases in collagen deposition; protein levels of type I and III collagens were significantly increased along with increases in their mRNA levels in the infarct area. This finding indicates that under myocardial infarction, Cu-dependent CCO activities were depressed but LOX activities were increased most likely through Cu redistribution although Cu concentrations were significantly depressed.
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PMID:Decreased copper concentrations but increased lysyl oxidase activity in ischemic hearts of rhesus monkeys. 2721 Feb 92