Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitors of apoptosis proteins (IAPs) are key intrinsic regulators of caspases-3 and -7. During ischemia, IAP-2 is upregulated dramatically, while the other IAPs show little or no change. To test whether IAP-2 prevents cardiac apoptosis and injury following ischemia/reperfusion, we generated a line of transgenic mice that carried a mouse IAP-2 transgene. High levels of mouse IAP-2 transcripts and 70 kDa IAP-2 were expressed in the hearts of transgenic mice, whereas IAP-1 and XIAP levels remained the same. Immunohistochemical studies revealed more intense staining of IAP-2 in the myocytes of transgenic mouse hearts. To assess the role of IAP-2 in I/R injury, the transgenic mice were subjected to ligation of the left descending anterior coronary artery ligation followed by reperfusion. The infarct sizes, expressed as the percentage of the area at risk, were significantly smaller in the transgenic mice than in the non-transgenic mice (30+/-2% vs. 44+/-2%, respectively, P<0.05). This protection was accompanied by a decrease of the serum level of troponin I in the transgenic mice. IAP-2 transgenic hearts had significantly fewer TUNEL-positive cardiac cells, which indicated an attenuation of apoptosis. Our results demonstrate that overexpression of IAP-2 renders the heart more resistant to apoptosis and I/R injury.
 ...
PMID:Overexpression of IAP-2 attenuates apoptosis and protects against myocardial ischemia/reperfusion injury in transgenic mice. 1732 13

The cardiac myofilaments are composed of highly ordered arrays of proteins that coordinate cardiac contraction and relaxation in response to the rhythmic waves of [Ca(2+)] during the cardiac cycle. Several cardiac disease states are associated with altered myofilament protein interactions that contribute to cardiac dysfunction. During acute myocardial ischemia, the sensitivity of the myofilaments to activating Ca(2+) is drastically reduced, largely due to the effects of intracellular acidosis on the contractile machinery. Myofilament Ca(2+) sensitivity remains compromised in post-ischemic or "stunned" myocardium even after complete restoration of blood flow and intracellular pH, likely because of covalent modifications of or proteolytic injury to contractile proteins. In contrast, myofilament Ca(2+) sensitivity can be increased in chronic heart failure, owing in part to decreased phosphorylation of troponin I, the inhibitory subunit of the troponin regulatory complex. We highlight, in this paper, the central role of the myofilaments in the pathophysiology of each of these distinct disease entities, with a particular focus on the molecular switch protein troponin I. We also discuss the beneficial effects of a genetically engineered cardiac troponin I, with a histidine button substitution at C-terminal residue 164, for a variety of pathophysiologic conditions, including hypoxia, ischemia, ischemia-reperfusion and chronic heart failure.
 ...
PMID:Tuning cardiac performance in ischemic heart disease and failure by modulating myofilament function. 1739 43

With cardiovascular (CV)-related disorders accounting for the highest mortality rates in the world, affecting the quantity and quality of life of patients and creating an economic burden of prolonged therapeutic intervention, there is great significance in understanding the cellular and molecular alterations that influence the progression of these pathologies. The cellular genotype is regulated by the DNA component, whilst the cellular phenotype is influenced by the protein complement. By improving the understanding of the molecular mechanisms that influence the protein profile, the pathologies that influence the intrinsic functions of the CV system may be detected earlier or managed more efficiently. This is achievable with technologies encompassed by 'proteomics.' Proteomic investigations of CV diseases, including dilated cardiomyopathy (DCM), atherosclerosis, and ischemia/reperfusion (I/R) injury, have identified candidate proteins altered with the pathologic states, complementing past biochemical and physiologic observations. Whilst proteomics is still a relatively new discipline to be applied to the basic scientific investigation of CV diseases, it is emerging as a technique to screen for potential biomarkers in both tissues/cells and biologic fluids (biofluids), as well as to identify the targets of existing therapeutics. By enabling the separation of complex mixtures over numerous dimensions, exploiting the intrinsic properties of proteins, including charge state, molecular mass, and hydrophobicity, in addition to cellular location, the discrete alterations within the cell may be resolved. Proteomics has shown alterations to myofilament proteins including troponin I and myosin light chain, correlating with the reduction in contractility in the myocardium from DCM and I/R. The diverse cell types that coalesce to induce atherosclerotic plaque formation have been investigated both collectively and individually to elucidate the influence of the modifications to single cell types on the developing plaque as a whole. Proteomics has also been used to observe changes to biofluids occurring with these pathologies, a new potential link between basic science and clinical applications. The development of CV proteomics has helped to identify a number of possible protein candidates, and offers the potential to treat and diagnose CV disease more effectively in the future.
 ...
PMID:Cardiovascular proteomics: past, present, and future. 1739 44

Previous studies indicate that adenosine supplementation or nitric oxide synthase (NOS) inhibition during reperfusion exert protective effects against myocardial ischemia-reperfusion (I/R) injury. We wanted to test the hypothesis that NOS inhibition before I/R also protects the myocardium against further injury and aimed to determine the involvement of adenosine receptors in a perfused rat heart model. Rats were injected with 10 mg/kg of L-NAME (N(omega)-nitro-L-arginine methyl ester) or L-NAME + SPT (8-(p-sulfophenyl)-theophylline)--an adenosine antagonist - at 2 x 25 mg/kg or with a saline buffer, 24 hrs prior to heart excision. The hearts, perfused retrogradely were subjected to 60 min of global ischemia followed by 120 min reperfusion. L-NAME decreased NOx (nitrite and nitrate) production (16.2 +/- 3.2 vs. 7.0 +/- 1.8 micromol/L; P<0.05) in vivo and increased the release of troponin I (0.04 +/- 0.01 vs. 0.02 +/- 0.01 microg/L; P<0.05) in the plasma, compared to controls. After 120 min of reperfusion, there was a higher release of adenosine (26.1 +/- 2.2 vs. 2.4 +/- 1.2 nmol/min; P<0.01) and a decrease in troponin I levels (0.19 +/-0.07 vs. 0.59 +/- 0.16 ng/min; P<0.05) in the L-NAME group compared to controls. These results were accompanied by a higher proportion of recovery of left ventricular developed pressure (72.0 +/- 4.0 vs. 60.0 +/- 4.0%; P<0.05) and coronary flow (72.0 +/- 5.0 vs. 51.0 +/- 4.0%; P<0.05) in the L-NAME group. These beneficial effects were not blocked by the adenosine receptor antagonist. The present study reveals that L-NAME protects against I/R injury when the inhibitor is administered 24 hrs before ischemia. The beneficial effects observed in this model appear to be independent of adenosine receptor stimulation.
 ...
PMID:Delayed 24 hours Nomega-nitro-L-arginine methyl ester injection induces pharmacological cardioprotection against reperfusion injury. 1754 24

Cardiovascular disease is the leading cause of perioperative morbidity and mortality after vascular surgery. The purpose of this study was to identify risk factors for myocardial ischemia after vascular surgery and to investigate a potential association of ischemia with mortality in a community hospital setting. A retrospective review was conducted after 190 major vascular procedures. Electrocardiogram (ECG) results and troponin I levels were obtained serially during the first 24 postoperative hours. Outcomes analyzed were ischemic ECG changes, troponin I level more than 2 ng/mL, 6-month mortality, and overall survival. The authors investigated any association of these outcomes with each other and the type of operation, history of coronary artery disease, diabetes, recent coronary intervention, age older than 70 years, or postoperative symptoms. Twenty-seven (14%) patients experienced ischemic ECG changes. Twenty-one (11%) patients experienced troponin I elevation. Univariate analysis revealed a history of coronary artery disease, diabetes, concerning symptoms, and troponin elevation to be predictive of ECG change (P < 0.05). ECG change and symptoms were predictive of troponin elevation (P < 0.01). Cox multivariate analysis revealed only infrainguinal bypass to predict 6-month mortality (odds ratio = 2.92, P = 0.02). Diabetes was the sole predictor of overall mortality (odds ratio = 1.94, P = 0.001). Nonsustained ischemic postoperative ECG changes during the first 24 postoperative hours do not independently influence 6-month or overall mortality after major vascular surgery. Postoperative troponin elevation likely conveys a mortality risk in the subsequent 6 months. In the community hospital setting, midterm survival rates after vascular surgery equivalent to those in higher volume centers can be achieved. Patients undergoing infrainguinal bypass and diabetics continue to be the most moribund vasculopaths.
 ...
PMID:Predictors of electrocardiographic change, cardiac troponin elevation, and survival after major vascular surgery: a community hospital experience. 1767 44

The presence, cause, and clinical significance of elevated cardiac troponin I in patients with acute lower limb ischemia is yet unknown. Forty-six patients (20 men [43%]; mean age 72 +/- 10 years, range 42 to 92) with acute lower limb ischemia were enrolled in this study. Serial creatine kinase (CK), CK isoenzyme MB (CK-MB), and troponin I measurements were obtained in all consecutive patients. Peak levels were evaluated for each patient. Twenty-four patients (52%) had elevated peak troponin I levels (>0.2 ng/ml) during their hospitalization. Patients were divided into 3 groups according to their peak troponin I levels: 11 patients (24%) had peak troponin I levels >1 ng/ml (the high troponin I group), 13 (28%) had levels of 0.2 to 1 ng/ml (the intermediate troponin I group), and the remaining 22 (48%) had peak troponin I levels <0.2 ng/ml (the low troponin I group). The peak CK levels were 10,263 +/- 16,513, 1,294 +/- 1,512, and 934 +/- 1,045 IU/ml (p = 0.04) in the 3 different troponin I subgroups, respectively, and the peak CK-MB levels were 143 +/- 170, 38 +/- 31, and 38 +/- 43, respectively (p = 0.04). Troponin I was positively correlated with CK (R = 0.35, p = 0.017) and CK-MB (R = 0.38, p = 0.009). The mean length of hospitalization was 8.3 +/- 6.2 days for the whole study group and did not vary among the 3 troponin I groups (10.5 +/- 10.9 vs 8.6 +/- 4.9 vs 7.2 +/- 4.0 days, p = 0.762). There were no differences in mortality during hospitalization among the 3 groups (4 of 11 vs 1 of 13 vs 4 of 22 patients, p = 0.22). In conclusion, patients with acute lower limb ischemia often have elevated cardiac troponin I levels. Elevated troponin I levels were not associated with the duration of hospitalization or with in-hospital mortality in this group of patients.
 ...
PMID:Cardiac troponin I in patients with acute lower limb ischemia. 1769 37

Matrix metalloproteinase (MMP)-2 mediates myocardial ischemia-reperfusion injury which is characterized by enhanced peroxynitrite biosynthesis during early reperfusion. Direct infusion of peroxynitrite into isolated hearts activates MMP-2 prior to the loss in mechanical function. The mechanical dysfunction is prevented by MMPs inhibitors. MMP-2 is also found in the sarcomere of cardiomyocytes where it cleaves troponin I and myosin light chain I. Cytoskeletal proteins such as alpha-actinin, desmin and spectrin are found in close association with the sarcomere and are known to be degraded in ischemia-reperfusion injury. It remains unknown whether these proteins are degraded in peroxynitrite-induced myocardial injury and if cytoskeletal proteins are also targets for MMP-2. Peroxynitrite (80 microM) was infused into isolated rat hearts which led to a delayed onset but rapidly developing decline in mechanical function. The MMPs inhibitor PD-166793 or the peroxynitrite scavenger glutathione prevented the decline in cardiac function. At the end of perfusion, alpha-actinin levels were decreased by 45+/-3% in peroxynitrite-infused hearts as compared to control hearts; however, this was normalized to that of control hearts with either PD-166793 or glutathione. Cardiac desmin and alphaII spectrin levels were unaltered following peroxynitrite infusion. alpha-Actinin and to a lesser extent desmin are susceptible to in vitro proteolysis by MMP-2 whereas spectrin is resistant. Cardiac dysfunction induced by peroxynitrite involves degradation of alpha-actinin that may be mediated by the proteolytic action of MMP-2.
 ...
PMID:Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. 1785 26

The case of a 24-year-old athlete who presented with a syncopal episode after having run 25 miles in a marathon is reported. The patient was subsequently found to have significant elevations of troponin I, which remained detectable for 3 days. The patient remained asymptomatic during his 8-day hospitalization without other evidence of cardiac ischemia: studies included echocardiography and multiple gated acquisition (MUGA) scan. The current knowledge about elevation of troponin I unrelated to cardiac injury in endurance athletes is discussed.
 ...
PMID:Elevation of troponin I in athletes: a case report in a marathon runner. 1797 96

Methylene blue (MB), generic name methylthioninium (C(16)H(18)ClN(3) S . 3H(2)O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. This effect has been attributed to MB's blocking effect on nitric oxide synthase and guanylyl cyclase, the latter blocking the synthesis of the second messenger of nitric oxide. The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100beta, as well as troponin I and creatine kinase isoenzyme MB, respectively.
 ...
PMID:Neuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue. 1807 76

The aim of this study was to establish cardiac damage related to nocturnal ischemia using heart type fatty acid binding protein (h-fabp), which reaches detectable levels in plasma after being released from myocytes in case of ischemia in obstructive sleep apnea syndrome (OSAS) patients without coronary artery disease (CAD). Fifty patients diagnosed with OSAS in our sleep laboratory with polysomnographic analysis (PSG), who did not have any previous history of cardiac disease and in whom CAD was ruled out with myocardium perfusion scintigraphy, were included in the study. Control group comprised 19 volunteers without history of cardiac disease and risk factors in whom OSAS was excluded with PSG analysis. Blood samples were drawn from the patients to examine h-fabp, creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), troponin I levels before and after sleep. No significant difference was found in CK, CK-MB, AST, Troponin I, and h-fabp levels before and after sleep in patient and control groups (p > 0.05). No significant difference was found between groups in terms of CK, CK-MB, AST, and Troponin I levels before and after sleep, while a significant difference was found between them with regard to h-fabp levels before (p = 0.006) and after sleep (p = 0.022). When arithmetical mean of the fabp levels before and after sleep was taken in the patient group, it was found that mean value of h-fabp was associated with the desaturated period in sleep which was under 80% (p = 0.04). H-fabp seems to be a marker that will enable the detection of cardiac injury in the early asymptomatic period in OSAS patients before development of disease that can be detected by imaging methods. Further studies are required to investigate the relation between the value of h-fabp and the development of cardiac dysfunction in the long term.
 ...
PMID:Evaluation of the relationship between heart type fatty acid binding protein levels and the risk of cardiac damage in patients with obstructive sleep apnea syndrome. 1823 25


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