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)

A plasma exchange program for familial hypercholesterolaemia was started in 1982. Ten patients aged from 7 to 58 years were progressively included: 3 had an heterozygous form of the disease with ischaemic heart disease; 3 had an homozygous form with defective low density lipoprotein receptor activity, 4 had a receptor-negative homozygous familial hypercholesterolaemia and had previously undergone portacaval shunt. During total plasma exchange against human albumin (470 sessions in 9 patients) low density lipoprotein cholesterol values, but also high density lipoprotein cholesterol values, decreased by 40 per cent. More recently, 5 patients had selective low density lipoprotein absorption on dextran sulfate column (Liposorber); 90 exchanges were performed. High density lipoprotein cholesterol values decreased by 55 per cent and high density lipoprotein cholesterol values by only 27 per cent. The patients' attitude to treatment was excellent, with less fatigue and better compliance.
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PMID:[Comparison between treatments of severe forms of familial hypercholesterolemia by total plasma exchange and selective removal of low density lipoproteins (LDLapheresis)]. 297 30

Diabetes mellitus is associated with severe and premature cardiovascular disease. The reasons for this have not been identified. It is now apparent that diabetics often have elevated circulating insulin levels compared to non-diabetics. In non-insulin dependent diabetes this is due to the associated obesity while in insulin treated diabetics exogenous insulin is responsible for hyperinsulinaemia between meals and at night. Two reports of high insulin levels in non-insulin dependent diabetics with cardiovascular disease are consistent with clinical and epidemiological studies linking hyperinsulinaemia with coronary, cerebral and peripheral arterial disease in non-diabetics. The arterial wall is an insulin sensitive tissue. Insulin promotes proliferation of arterial smooth muscle cells and enhances lipid synthesis and low density lipoprotein receptor activity. Insulin also promotes experimental atherosclerosis in a number of species. The evidence linking hyperinsulinaemia to the cardiovascular complications and diabetes is suggestive but incomplete and much more information on predictive factors for arterial disease in diabetes is urgently required. Diabetes mellitus is associated with severe and premature cardiovascular disease (reviewed by Stout 1982). Ischaemic heart disease, stroke and peripheral vascular disease are all more common in diabetics, particularly diabetic women. Although there is evidence for the existance of a specific diabetic cardiomyopathy, much of the cardiovascular disease in diabetics is due to atherosclerosis and its complications. Arterial disease in diabetics in distinct from microvascular disease affecting capillaries, and does not differ morphologically or biochemically from atherosclerosis in non-diabetics. The reason for the increased incidence of atherosclerosis in diabetes has not been established. Both non-insulin dependent and insulin dependent diabetes appear to be associated with cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperinsulinaemia--a possible risk factor for cardiovascular disease in diabetes mellitus. 390 79

Hypercholesterolemia is a primary risk factor for atherosclerosis, coronary artery disease, and myocardial infarction. We subjected low density lipoprotein receptor-deficient (LDLr -/-) and control (wild-type) mice to 30 minutes of myocardial ischemia and 120 minutes of reperfusion. Myocardial infarction per area at risk (AAR) was noted under baseline conditions to be significantly (P<0.05) smaller in the LDLr -/- mice compared with wild-type mice (24.7+/-3. 2% and 38.8+/-4.3% of AAR, respectively). Subsequently, mice were fed a high-cholesterol diet (HCD) for 2 or 12 weeks, which resulted in significant increases in serum cholesterol levels in both LDLr -/- and wild-type groups. After 2 weeks of the HCD, the LDLr -/- mice demonstrated a significant elevation (P<0.01) in myocardial necrosis per AAR (50.2+/-5.36% of AAR) compared with the normal-diet LDLr -/- group, whereas the short-term HCD-fed wild-type mice demonstrated no significant difference from baseline. In contrast, wild-type mice fed the HCD for 12 weeks revealed a significant (P<0. 05) decrease in necrosis per AAR, which was 22.5+/-3.2% of the AAR in comparison with that in the normal-diet wild-type mice (38.8+/-4. 3% of AAR). LDLr -/- mice on the same long-term HCD showed a similar significantly (P<0.05) decreased infarct size, which was 13.2+/-4.0% of the AAR. In additional experiments, we determined that myocardial tissue total glutathione (GSH) levels were reduced after 2 weeks of the HCD and were significantly increased after 12 weeks of the HCD in the LDLr -/- mouse heart. These data suggest that short-term cholesterol feeding renders the myocardium of LDLr -/- mice more susceptible to ischemia-reperfusion injury, whereas more long-term hypercholesterolemia confers cardioprotection in the LDLr -/- mouse heart.
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PMID:Effects of hypercholesterolemia on myocardial ischemia-reperfusion injury in LDL receptor-deficient mice. 1055 25

Individuals with a heterozygous mutation at the ataxia-telangiectasia mutated gene (ATM) have been reported to be predisposed to ischemic heart disease. This report examined for the first time the effect of a heterozygous ATM mutation (ATM(+)(/-)) on plasma lipid levels and atherosclerosis intensity using ATM(+/-), ATM(+)(/+) (wild type), ATM(+)(/+)/LDLR(-)(/-) (low density lipoprotein receptor knockout), ATM(+)(/-)/LDLR(-)(/-), ATM(+)(/+)/ApoE(-)(/-) (apolipoprotein E knockout), and ATM(+)(/-)/ApoE(-)(/-) mice. Our data demonstrated that the plasma cholesterol and triglyceride levels in ATM(+)(/-) and ATM(+)(/-)/LDLR(-)(/-) mice were approximately the same as those in ATM(+)(/+) and ATM(+)(/+)/LDLR(-)(/-) control mice, respectively. In contrast, the plasma cholesterol level was significantly higher in ATM(+)(/-)/ApoE(-)(/-) mice than in ATM(+)(/+)/ApoE(-)(/-) control mice. In addition, the ATM(+)(/-)/ApoE(-)(/-) mice showed higher plasma apoB-48 levels, slower clearance for plasma apoB-48-carrying lipoproteins, and more advanced atherosclerotic lesions in the aorta compared with the ATM(+)(/+)/ApoE(-)(/-) mice. These novel results suggest that the product of ATM is involved in an apoE-independent pathway for catabolism of apoB-48-carrying remnants; therefore, superimposition of a heterozygous ATM mutation onto an ApoE deficiency background reduces the clearance of apoB-48-carrying lipoproteins from the blood circulation and promotes the formation of atherosclerosis.
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PMID:Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice. 1586 39

Advanced atherosclerosis, through thrombosis, leads to ischemic heart disease and ischemic stroke, the leading causes of death and disability worldwide. Advanced atherosclerosis and imaging of atherosclerosis are the focus of this dissertation with particular emphasis on the vulnerable plaque and vulnerable plaque detection. Aspects of advanced atherosclerosis and the vulnerable plaque in humans are described along with the basis for the selected minipig models and methods for atherosclerosis acceleration used. The overall aims of the studies were to develop an animal model of advanced atherosclerosis with human like vulnerable plaque morphology and use this animal model to test an imaging modality aimed at vulnerable plaque detection. The first aim is addressed in 3 papers, where accelerated plaque development in the coronary and carotid arteries is investigated in down sized Rapacz pigs. Down-sized Rapacz pigs are minipigs with familial hypercholesterolemia caused by a mutation in the low density lipoprotein receptor. Paper 1 describes the lipid profile in the down-sized Rapacz on chow and atherogenic diets and spontaneously developed and balloon accelerated coronary plaque with a morphology that resembles the morphology of human vulnerable plaque. Paper 2 describes vein graft disease in internal jugular vein grafts inserted into the common carotid artery. Plaques with necrotic cores were found in oversized vein grafts only indicating an effect of flow and shear stress on plaque development. Paper 3 describes the effects of wall shear stress on local plaque development in surgically stenosed common carotid arteries in the down-sized Rapacz pigs. This study indicated that the combination of low and oscillatory wall shear stress was needed for development of advanced plaque. In paper 4, we interrogated coronary lesions in the down-sized Rapacz with a commercially available diagnostic tool VH IVUS. It is claimed that VH IVUS can characterize the tissue components that constitute plaque reliably. However, we found that VH IVUS does not reliably assess the most important plaque component of all, i.e. the necrotic core. In conclusion, we developed an animal model of advanced atherosclerosis with human like vulnerable plaque morphology. The usefulness of this animal model was demonstrated in a study testing an imaging modality aimed at vulnerable plaque detection in humans.
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PMID:Human-like atherosclerosis in minipigs: a new model for detection and treatment of vulnerable plaques. 2059 44

Myocardial ischemia is associated with intracellular accumulation of lipids and increased depots of myocardial lipids are linked to decreased heart function. Despite investigations in cell culture and animal models, there is little data available on where in the heart the lipids accumulate after myocardial ischemia and which lipid species that accumulate. The aim of this study was to investigate derangements of lipid metabolism that are associated with myocardial ischemia in a porcine model of ischemia and reperfusion. The large pig heart enables the separation of the infarct area with irreversible injury from the area at risk with reversible injury and the unaffected control area. The surviving myocardium bordering the infarct is exposed to mild ischemia and is stressed, but remains viable. We found that cholesteryl esters accumulated in the infarct area as well as in the bordering myocardium. In addition, we found that expression of the low density lipoprotein receptor (LDLr) and the low density lipoprotein receptor-related protein 1 (LRP1) was up-regulated, suggesting that choleteryl ester uptake is mediated via these receptors. Furthermore, we found increased ceramide accumulation, inflammation and endoplasmatic reticulum (ER) stress in the infarcted area of the pig heart. In addition, we found increased levels of inflammation and ER stress in the myocardium bordering the infarct area. Our results indicate that lipid accumulation in the heart is one of the metabolic derangements remaining after ischemia, even in the myocardium bordering the infarct area. Normalizing lipid levels in the myocardium after ischemia would likely improve myocardial function and should therefore be considered as a target for treatment.
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PMID:Cholesteryl esters accumulate in the heart in a porcine model of ischemia and reperfusion. 2363 33