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

Understanding of the pathophysiology of atherosclerosis has changed markedly over the past few decades. It is now widely accepted that inflammation plays a fundamental role in the genesis and development of atherosclerosis. Inflammatory mechanisms also appear to determine clinical presentation and disease outcome. Atherosclerotic lesions have high concentrations of inflammatory cells (T lymphocytes and activated macrophages) as well as an abundance of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-8, interferon-gamma, tumor necrosis factor-alpha, etc.] that modulate local inflammatory responses. These may also alter plaque stability and facilitate the development of acute cardiovascular events. The role of anti-inflammatory cytokines in this context remains to be studied. IL-10 is an anti-inflammatory cytokine synthesised by T-lymphocytes and macrophages and has other anti-inflammatory effects. IL-10 expression within human atherosclerotic plaques has been demonstrated and animal experiments have shown that low levels of IL-10 lead to the development of extensive and unstable atherosclerotic lesions. Currently available evidence suggests a potential protective role for IL-10 in atherosclerosis. This new perspective on coronary disease as a chronic inflammatory process may open new avenues for the management of ischemic heart disease.
 ...
PMID:[Interleukin-10 and coronary disease]. 1211 2

Fas ligand (FasL) is a member of tumor necrosis factor family that induces apoptosis in target cells that express Fas. The function of FasL during inflammation remains controversial. In this study, we examined the role of vascular endothelial FasL during acute myocardial ischemia-reperfusion that is closely associated with inflammation. Transgenic mouse lines were established that overexpress human FasL on endothelium under the control of the vascular endothelial cadherin promoter. Expression of FasL transgene was detected at both mRNA and protein levels, and functional transgene-encoded FasL protein was specifically expressed on the surface of vascular endothelial cells. Transgenic mice developed normally and had normal hearts. When subjected to 30 min of myocardial ischemia and 72 h of reperfusion, myocardial infarct size was reduced by 42% in the transgenic mice compared with nontransgenic littermates (p < 0.05). Moreover, hemodynamic data demonstrated that transgenic hearts performed better following ischemia and reperfusion compared with nontransgenic hearts. Myocardial neutrophil infiltration was reduced by 54% after 6 h of reperfusion in transgenic hearts (p < 0.01). Neutrophil depletion prior to ischemia-reperfusion injury led to smaller infarcts that were not different between transgenic and nontransgenic mice, suggesting that endothelial FasL may attenuate ischemia-reperfusion injury by abating the inflammatory response. These results indicate that vascular endothelial FasL may exert potent anti-inflammatory actions in the setting of myocardial ischemia-reperfusion injury.
 ...
PMID:Endothelial cell overexpression of fas ligand attenuates ischemia-reperfusion injury in the heart. 1257 84

The phenotypic and functional changes of coronary arteries with aging promote ischemic heart disease. We hypothesized that these alterations reflect an aging-induced proinflammatory shift in vascular regulatory mechanisms. Thus, in isolated coronary arteries of young (3-month-old) and aged (25-month-old) male Fischer 344 rats the expression of 96 cytokines, chemokines, and their receptors were screened by a cDNA-based microarray technique. In aged vessels expressions of tumor necrosis factor (TNF)-alpha (3.3x), interleukin (IL)-1beta (3.0x), IL-6 (2.9x), IL-6Ralpha (2.8x) and IL-17 (6.1x) genes were significantly increased over young vessels. Quantitative reverse transcriptase-polymerase chain reaction confirmed these results. Western blotting demonstrated that protein expressions of TNF-alpha, IL-1beta, IL-6, and IL-17 were also significantly increased in vessels of aged rats compared with those of young rats. Immunofluorescent double labeling showed that in aged vessels IL-1beta and IL-6 are predominantly localized in the endothelium, whereas TNF-alpha and IL-17 are localized in smooth muscle. Thus, a proinflammatory shift in the profile of vascular cytokine expression may contribute to the aging-induced phenotypic changes in coronary arteries, promoting the development of ischemic heart disease in the elderly.
 ...
PMID:Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. 1270 2

Cardiomyocytes are post-mitotic, long-lived cells until disruptions to pro-survival factors occur after myocardial ischemia. To gain an understanding of the factors involved with ischemic injury, we examined expression changes in pro-survival and opposing pro-apoptotic signals at early and chronic periods of ischemia using an in vivo murine model. Alterations of pro-survival proteins such as the inhibitor of apoptosis protein on chromosome X (xIAP) and the apoptotic repressor protein (ARC) have not been evaluated in a murine model of cardiac ischemia. Early ischemia (1 day) resulted in a 50% reduction in ARC protein levels relative to sham-operated left ventricles, without significant changes in the expression of xIAP or other pro-survival factors. In contrast, a deficiency of xIAP expression was found in cardiac infarcts starting after 1 week, concomitant with significant evidence of apoptotic cell death and an up-regulation of pro-apoptotic signals including Bax, tumor necrosis factor-a, and caspase-8 activation. Chronic ischemia (after 2 weeks) was associated with elevated levels of other pro-survival factors such as Bcl-xL and the phosphorylated form of Akt, as part of the adaptive remodeling of the myocardium. Altogether, these findings suggest that strategies to increase IAP expression may promote myocyte survival after chronic ischemia.
 ...
PMID:Ischemia elicits a coordinated expression of pro-survival proteins in mouse myocardium. 1280 54

To analyze the protective effects of the aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024), a compound endowed with DA2-dopaminergic/alpha2-adrenergic receptor agonistic activity, in myocardial ischemia/reperfusion damage. A model of isolated and perfused (15 ml/min) electrically driven (300 beats/min) rat heart subjected to global ischemia (1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min) was followed. Cardiac mechanics changes were evaluated together with biochemical markers of cardiac ischemia in perfusate and tissue tumor necrosis factor-alpha (TNF-alpha). CHF-1024, perfused through the heart for 15 min before ischemia at different molar concentrations (1-100 nM), significantly improved left ventricle developed pressure during reperfusion, and normalized left ventricular end-diastolic pressure and coronary perfusion pressure. This anti-ischemic effect of CHF-1024 was associated to a decrease in creatine kinase and lactate dehydrogenase, both released during heart reperfusion. These events were concomitant with maintenance of a higher production of 6-keto-prostaglandin F1alpha The ability of CHF-1024 to improve postischemic ventricular dysfunction was correlated with a dose-dependent inhibition of the release of both norepinephrine (NE), from sympathetic nerve endings, and TNF-alpha from cardiac tissue. The effect of CHF-1024 on NE release was almost completely antagonized by specific antagonists of presynaptic inhibitory receptors domperidone and rauwolscine. The finding that this new aminotetraline derivative possesses anti-ischemic properties and limits NE release from cardiac nerve endings may bear some therapeutic potential in cardiovascular diseases.
 ...
PMID:The aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024) displays cardioprotection in postischemic ventricular dysfunction of the rat heart. 1297 93

Human high-density lipoproteins (HDLs) protect the heart against ischemia/reperfusion injury. In the present study, the cardioprotective effects of synthetic high-density lipoproteins (sHDLs) made of phosphatidylcholine and apolipoprotein A-I were investigated in isolated rat hearts, which underwent a 20-min low-flow ischemia followed by a 30-min reperfusion. The administration of sHDL during the 10 min immediately before ischemia caused a rapid, dose-dependent improvement of postischemic cardiac function: at the maximum dose (2.0 mg of sHDL protein/ml), left ventricular developed pressure (LVDP) recovered to 71.0 +/- 3.2 versus 40.5 +/- 3.8 mm Hg in saline-treated hearts, and coronary perfusion pressure (CPP) increased to 100.3 +/- 6.2 versus 132.0 +/- 9.0 mm Hg. The preservation of postischemic cardiac function was associated with a dose-dependent reduction of creatine kinase release into the coronary effluent. sHDLs administered in the first 10 min postischemia also exerted a significant, dose-dependent improvement of postischemic LVDP, CPP, and creatine kinase release, but the cardioprotective effect was less than when sHDLs were given preischemia. The preservation of postischemic cardiac function by sHDL was mediated through a reduction of cardiac tumor necrosis factor-alpha content and an enhanced cardiac production of prostaglandin E2 and I2. The present experimental data indicate that sHDLs may provide a novel therapeutic approach to clinical conditions in which myocardial ischemia/reperfusion occurs, such as acute coronary syndromes, cardiac surgery, or revascularization procedures.
 ...
PMID:Synthetic high-density lipoproteins exert cardioprotective effects in myocardial ischemia/reperfusion injury. 1456 9

There is epidemiologic evidence that the prognosis of patients with nonischemic heart failure is better than that for patients with ischemic heart failure. In addition, studies have revealed that patients with ischemic heart failure show a poorer response to medical therapy. However, the pathophysiologic difference between ischemic and nonischemic heart disease is unclear. To clarify this point, we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in plasma and pericardial fluid in patients with ischemic or nonischemic heart disease undergoing cardiac surgery. The pericardial ET-1 concentration in patients with ischemic heart disease was statistically greater than that in patients with nonischemic heart disease (about 1.5-fold), although no difference was found in the plasma ET-1 concentration. These findings suggest that the production and secretion of ET-1 from the myocardium in patients with ischemic heart disease are augmented to a greater extent than in patients with nonischemic heart disease. This result may lead to a greater understanding of the pathophysiology of ischemic heart disease.
 ...
PMID:Endothelin-1 concentrations in pericardial fluid are more elevated in patients with ischemic heart disease than in patients with nonischemic heart disease. 1458 45

Recent evidence associates inflammatory mediators with coronary heart disease. Elevation of acute-phase reaction (APR) proteins such as serum amyloid A, fibrinogen, CRP and haptoglobin in response to Helicobacter pylori (H. pylori) infection was shown to initiate gastritis and ischemic heart disease. Positive Chlamydia pneumoniae (C. pneumoniae) serology is associated with increased levels of inflammatory cytokines and tumor necrosis factor-alpha (TNF-alpha), which stimulates endothelial cell activation, procoagulant activity and angiogenesis in patients with coronary heart disease. As a final example, interleukin-6 (IL-6) has been proposed to mediate cardiovascular disorders. Public awareness of risks of excessive body weight and high levels of serum cholesterol propelled the development of synthetic dietary components such as sucrose polyester (SPE) to substitute for natural lipids. SPE is a synthetic lipid whose physical properties are similar to a natural triacylglycerol with a similar assortment of fatty acids and is resistant to lipolysis by gastric and pancreatic enzymes. Intake of SPE in lieu of natural lipids is expected to decrease absorption of essential fatty acids (EFA) and fat-soluble vitamins among other essentials. Deficiency of EFA leads to the formation of faulty cellular membranes, which is manifested as skin lesions, growth failure, erythrocyte fragility, impairment of fertility and uncoupling of oxidation and phosphorylation. Possibilities of absorption of these synthetic lipids into the circulation may represent an unexpected health hazard. We have shown that subcutaneous (sc) administration to rabbits of a range of lipolysis-resistant lipid-like sorbitol, mannitol and arabitol esters of palmitic (P) and lauric (L) acids was found to evoke a mild APR, which in humans could contribute to CHD incidence. We suggest a reversal in the commonly accepted role of SPE as a sequestor of dietary lipid: SPE may be the lipophilic solute contained within the dietary lipid solvent micelle. An alternative conclusion regarding the biological effects of excessive dose of SPE in human and pig for a short time span should be considered.
 ...
PMID:Cardiac heart disease in the era of sucrose polyester, Helicobacter pylori and Chlamydia pneumoniae. 1496 37

Among the cardiovascular pathologies, ischemic heart disease is the leading cause of congestive heart failure as well as permanent premature disabilities. Reperfusion of a previously ischemic heart is a standard clinical procedure. Even if beneficial, reperfusion triggers an inflammatory response that contributes to the acute extension of ischemic injury and later participates in the reparative processes of the damaged myocardium. Occlusion of a major coronary artery in small rodents, followed or not followed by reperfusion, has proven to be a good model to assess the relevance of pathophysiological processes and drug effects in the setting of myocardial ischemia. Models involving reperfusion appear to be particularly suitable to study the inflammatory response, which is much more marked than with permanent ischemia. Ischemia/reperfusion of the myocardium in wild-type and transgenic animals (mostly mice) allows the possibility of testing the vast array of mediators that orchestrate the sequelae of inflammation, including tumor necrosis factor (TNF). Moreover, this model allows testing of the protective effects of anti-inflammatory drugs in experimental myocardial infarction.
 ...
PMID:Myocardial infarction: animal models. 1506 43

A possible role of palmitic acid/Ca2+ (PA/Ca2+) complexes in the cyclosporin-insensitive permeability transition in mitochondria has been studied. It has been shown that in the presence of Ca2+, PA induces a swelling of mitochondria, which is not inhibited by cyclosporin A. The swelling is accompanied by a drop in membrane potential, which cannot be explained only by a work of the Ca2+ uniporter. With time, the potential is restored. Evidence has been obtained indicating that the specific content of mitochondrial lipids would favor the PA/Ca2+ -induced permeabilization of the membrane. In experiments with liposomes, the PA/Ca2+ -induced membrane permeabilization was larger for liposomes formed from the mitochondrial lipids, as compared to the azolectin liposomes. Additionally, it has been found that in mitochondria of the TNF (tumor necrosis factor)-sensitive cells (WEHI-164 line), the content of PA is larger than in mitochondria of the TNF-insensitive cells (C6 line), with this difference being mainly provided by PA incorporated in phosphatidylethanolamine and especially, cardiolipin. The PA/Ca2+ -dependent mechanism of permeability transition in mitochondria might be related to some pathologies, e.g. myocardial ischemia. The heaviness of myocardial infarction of ischemic patients has been demonstrated to correlate directly with the content of PA in the human blood serum.
 ...
PMID:Formation of palmitic acid/Ca2+ complexes in the mitochondrial membrane: a possible role in the cyclosporin-insensitive permeability transition. 1522 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>