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)

After certain periods of myocardial ischemia and reperfusion, cardiac dysfunction exists in the absence of myonecrosis. In a blood-perfused isolated rat heart model, we have demonstrated early gene changes that are associated with global myocardial "stunning." Early gene changes included elevations in the expression of messenger RNAs for HSP70, c-myc and c-fos. Increased expression of messenger RNAs for protooncogenes is an important observation because of the role of protooncogenes as nuclear transcription factors. From these study findings, it would appear that the stunning state is associated with early gene changes that may signal the induction of a hypertrophic process. Subsequent studies are required to demonstrate the exact events which take place in the course of stunning that directly initiate an alteration in gene expression.
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PMID:Early gene changes in myocardial ischemia. 794 6

Regional and global myocardial ischemia and reperfusion have been demonstrated to induce expression of the stress response protein heat shock 70 (HSP70) and of immediate early genes, c-jun, c-fos, and c-myc. Because of the models that have been utilized, it has not been possible to discriminate whether this response is the consequence of ischemia, reperfusion, or abnormal hemodynamic stress superimposed on stunned myocardium. In a nonworking isolated and blood-perfused rat heart model, we evaluated the mRNAs for c-fos, c-myc, and hsp70. The heart was subjected to varying periods of ischemia and reperfusion. Significant increases in hsp70 and c-fos were observed, which increased with longer periods of ischemia. No significant increase in c-myc was measured. In addition, mRNA encoding the Ca2+/glucose responsive stress protein GRP78 was evaluated. No increase in this early response gene was noted despite the use of a model associated with cellular calcium loading. Based on these observations, we suggest that the induction of hsp70 and c-fos is the consequence of ischemia and reperfusion and not dependent upon an early hypertrophy response such as would be observed in afterload mismatching or on calcium loading. Further investigations are necessary to isolate the effects of ischemia from those of reperfusion.
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PMID:Myocardial stunning: association with altered gene expression. 806 49

Emotional stress is considered to be one of the etiological factors in ischemic heart disease (IHD) and sudden cardiac death (SCD), mechanisms of which are poorly understood. Immediate early genes (IEGs), such as c-fos and c-jun are used as tools for detection of cellular activation. Male Wistar rats were exposed to acute immobilization (IMO). IMO stress for 30 min induced c-fos and c-jun mRNAs expression in the myocardium and the smooth muscle layer of the coronary arteries. IMO stress for 2 h also induced Fos and Jun like-immunoreactivities in the same regions. Distribution of IEG mRNAs and their protein products in the myocardium was not uniform but rather localized. These data provided histological evidence for an early cellular event in the stress response whose consequences could result in activation of tissues in the myocardium and coronary arterial smooth muscle cells which play a role in the pathophysiological changes in IHD and SCD.
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PMID:Immobilization stress induces c-fos and c-jun immediate early genes expression in the heart. 876 Oct 6

Chagas' disease, caused by the parasite Trypanosoma cruzi, is an important cause of heart disease. Previous studies from this laboratory revealed that microvascular spasm and myocardial ischemia were observed in infected mice. Infection of endothelial cells with this parasite increased the synthesis of biologically active endothelin-1 (ET-1). Therefore. in the myocardium of T. cruzi-infected mice, we examined ET-1 expression and the p42/44-mitogen activated protein kinase (MAPK)-AP-1 pathway that regulates the expression of ET-1. There was parasitism and myonecrosis in the myocardium of infected C57BL/6 mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed elevated mRNA expression of transcription factor AP-1 (c-jun and c-fos) and increased AP-1 DNA binding activity as determined by electrophoretic mobility shift assay (EMSA). Western blot analysis demonstrated an increase in the phosphorylated forms of extracellular signal-regulated kinase (ERK1/2). ET-1 mRNA was upregulated in the myocardium of infected mice. Immunohistochemical and immunoelectron microscopy using anti-ET-1 antibody detected increased expression in cardiac myocytes and endothelium of these mice. These data suggest that ET-1 contributes to chagasic cardiomyopathy and that the mechanism of the increased expression of ET-1 is a result of the activation of the MAPK pathway by T. cruzi infection.
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PMID:Trypanosoma cruzi infection (Chagas' disease) of mice causes activation of the mitogen-activated protein kinase cascade and expression of endothelin-1 in the myocardium. 1107 62

In isolated, perfused adult rat hearts, global ischemia increased the phosphorylation of cAMP response element-binding protein (CREB) relative to control levels, and this phosphorylation was reversed with reperfusion. CREB phosphorylation elicited by 5 min of global ischemia was sensitive to treatments with the calcium-independent phospholipase A(2) (iPLA(2)) inhibitor bromoenol lactone (BEL) and occurred in the absence of increases in myocardial cAMP content. In contrast, CREB phosphorylation elicited by 15 min of global ischemia was likely mediated by elevated cAMP levels. The expression of c-fos, in response to brief myocardial ischemia, was also sensitive to BEL treatment. The induction of iPLA(2)-mediated CREB phosphorylation was further substantiated by the observations that lysoplasmenylcholine increased both the phosphorylation of CREB and the induction of c-fos expression in the absence and presence of BEL. CREB phosphorylation in both ischemic hearts and lysoplasmenylcholine-perfused hearts was inhibited by pretreatment of hearts with the specific cAMP-dependent protein kinase (PKA) inhibitor H-89. Taken together, these data demonstrate that iPLA(2) mediates CREB phosphorylation through a PKA-dependent pathway during brief periods of myocardial ischemia, possibly through the formation of lysophospholipids.
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PMID:Calcium-independent phospholipase A(2) mediates CREB phosphorylation and c-fos expression during ischemia. 1140 82

Previously we showed that cardiac fibroblasts are cellular targets of estrogen and that there are significant differences in proliferative response of male and female cardiac fibroblasts under hypoxia, a condition of myocardial ischemia. Here, we tested the hypothesis that signaling pathways that control cell cycle progression and apoptosis in cardiac fibroblasts may be activated in a gender-specific manner. Cardiac fibroblasts from adult, age-matched male and female rat heart were exposed to hypoxia (2% O2) and normoxia. Western analysis of cell lysate was used to compare the level of basal and hypoxia-induced expression of signal transduction proteins, known to control cell cycle progression and cell death. Hypoxia led to significant activation of MAP (mitogen-activated protein) kinase and Jun kinase pathways, as shown by phosphorylated extracellular signal-regulated kinase (ERK1/2) and Jun kinase isotypes in male cells but this effect was modest in female cells. Male cells expressed higher levels of basal expression for transcription factors c-jun and NF-kB as well as the inhibitor of NF-kB (lk-B). Although hypoxia did not induce changes in the level of c-Jun in either cell type, it moderately increased the level of NF-kB in male cells but led to its decrease in female cells. Basal and hypoxia-induced expression of cyclin D1, c-fos, and PCNA seemed to be comparable in both male and female cells. However, hypoxia-induced activation of cyclin B1, which occurred in both cells, was stronger in female cells. Basal expression of apoptosis-associated transcription factor, p53, was comparable in both cells. However, under hypoxia, there was an increase in the p53 level only in female cells. Although female cells showed higher basal expression for survival-associated protein, Bcl-2, the level of this protein remained unchanged under hypoxia in both cells. Together, these data demonstrate differences in basal and hypoxia-induced expression of proteins with an established role in cell cycle progression and apoptosis in male and female cardiac fibroblasts. These differences may further point to gender-related differences in signal transduction pathways that control the proliferative response of those cells under hypoxia.
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PMID:Gender-related differences in basal and hypoxia-induced activation of signal transduction pathways controlling cell cycle progression and apoptosis, in cardiac fibroblasts. 1237 61

To investigate law of FOS protein induced by myocardial ischemia reperfusion (MI/R) in acute period, a model in 20 anaethetized SD rats was established. Rats with normal and ischemia were used as control groups. Specimens were studied immunohistochemically with c-fos antibody. After ischemia 20 minutes, followed by 30 minutes reperfusion, the area of MI/R showed nuclei of myocytes positive staining in cryosection slides. In C2 group, the area showed nuclei of myocytes (37.76% +/- 9.66%) positive staining weakly. In C3 group, nuclei of cardiac myocytes(40.34% +/- 3.32%) was significantly positive. In C4 group it began to attenuate(35.36% +/- 4.81%). The myocardium in normal and ischemic control groups showed negative staining. No changes were seen with HE staining. Our data indicated that immunohistochemical method may reveal acute MI/R injury of ischemia 20 min and reperfusion 30 min with anti-FOS protein staining and there is problely a peak between 60-120 min after reperfusion. It is possible that the method be used to diagnose sudden cardiac death in forensic medicine.
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PMID:[Immunohistochemical study on myocardial acute ischemia reperfusion injury in rats with anti-FOS protein antibody]. 1253 30

Free radicals and oxidative stress play a crucial role in the pathophysiology of a broad spectrum of cardiovascular diseases including congestive heart failure, valvular heart disease, cardiomyopathy, hypertrophy, atherosclerosis and ischemic heart disease. We have demonstrated that IH636 grape seed proanthocyanidin extract (GSPE) provides superior antioxidant efficacy as compared to Vitamins C, E and beta-carotene. A series of studies were conducted using GSPE to demonstrate its cardioprotective ability in animals and humans. GSPE supplementation improved cardiac functional assessment including post-ischemic left ventricular function, reduced myocardial infarct size, reduced ventricular fibrillation (VF) and tachycardia, decreased the amount of reactive oxygen species (ROS) as detected by ESR spectroscopy and reduced malondialdehyde (MDA) formation in the heart perfusate. Cardiomyocyte apoptosis detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining. In concert, the proapoptotic signals mediated by JNK-l and c-fos proteins were also reduced suggesting that the novel cardioprotective properties of GSPE may be at least partially attributed to its ability to block anti-death signaling mediated through the proapoptotic transcription factors and genes such as JNK-1 and c-JUN. In a separate study, GSPE pretreatment significantly inhibited doxorubicin-induced cardiotoxicity as demonstrated by reduced serum creatine kinase (CK) activity, DNA damage and histopathological changes in the cardiac tissue of mice. Concentration-dependent efficacy of GSPE was also assessed in a hamster atherosclerosis model. Approximately 49 and 63% reduction in foam cells, a biomarker of early stage atherosclerosis, were observed following supplementation of 50 and 100 mg GSPE/kg body weight, respectively. A human clinical trial was conducted on hypercholesterolemic subjects. GSPE supplementation significantly reduced oxidized LDL, a biomarker of cardiovascular diseases. Finally, a cDNA microarray study demonstrated significant inhibition of inducible endothelial CD36 expression, a novel cardioregulatory gene, by GSPE. These results demonstrate that GSPE may serve as a potential therapeutic tool in promoting cardiovascular health via a number of novel mechanisms.
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PMID:Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. 1262 6

Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.
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PMID:Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: possible links to hypertension, atherogenesis, and stroke. 1294 25

Angina pectoris is important because of its association with heart disease and risk of death. Historically after Heberden's account of angina in 1772, the association of pain with coronary artery disease quickly followed. Within a few years, Burns suggested an etiological role for ischemia. Subsequently, theories of differential myocardial stretch dominated thinking until Lewis' chemical hypothesis in 1932, in which the local release of chemical substances during ischemia was seen as the cause of pain. This review considers how ischemia at the tissue level triggers activation of afferent nociceptive pain fibres. The afferent projections of sympathetic and vagal afferent fibres are described, with a number of methodologies cited (eg, injection of pseudorabies virus into the heart with mapping of the retrograde viral transport pathways; and elevation of neuronal c-fos synthesis in brain regions activated by capsaicin application to the heart). Our own functional neuroimaging studies of angina are also reviewed. There are 2 intriguing features of angina. The first is the poor correlation between symptoms and extent of coronary disease. The spectrum ranges from entirely silent myocardial ischemia to that of a functional pain syndrome--the 'sensitive heart'--of cardiac syndrome X. An even more difficult aspect is the wide variability in symptoms experienced by an individual patient. A new paradigm is presented which, besides considering myocardial oxygen supply/demand imbalance, also draws insights from the broader field of pain research. Neuromodulation applies at multiple levels of the neuraxis--peripheral nerves, spinal cord, and brain--and it invites exploitation, whether pharmacological or electrical, for the benefit of the cardiac patient in pain.
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PMID:From heart to brain: the genesis and processing of cardiac pain. 2242 86


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