Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heart disease in older individuals can be characterised as the result of 2 processes, hypertension and atherosclerosis, which are the major causes of heart failure in the elderly population. The aging heart undergoes changes at the molecular, cellular and organ levels. These age-related changes may then be modulated by pathological conditions, such as hypertension, and by the reduction of blood pressure. One characteristic of the aged heart is a limited capacity for adaptation, by hypertrophy, to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun. This diminution results from aging of the heart per se and may be modulated by extracardiac factors. With regard to the coronary vasculature, the age at which hypertension develops seems to be an important factor for determining the vascularity of hypertrophied hearts. Late-onset hypertension is not accompanied by coronary angiogenesis, and it decreases dilator reserve in spite of the absence of myocardial hypertrophy. In contrast, mechanical overload in infant hearts is accompanied by angiogenesis and normal dilator reserve. In principle, the normalisation of hypertension results in the regression of myocardial hypertrophy and decreased coronary dilator reserve. In aged hearts, it is not clear how hypertension-induced myocardial hypertrophy or coronary vascular changes regress. Although antihypertensive treatment is clearly associated with an improvement of cardiovascular mortality and morbidity in hypertensive elderly individuals, it remains unclear how treatments ameliorate the hypertension-induced alterations.
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PMID:Hypertension and age-related changes in the heart. Implications for drug therapy. 798 82

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

Diseases of the heart are the No. 1 killer in industrialized countries. Brain injury can develop as a result of cerebral ischemia-reperfusion due to stroke (brain attack) and other cardiovascular diseases. Learning about the disease is the best way to reduce disability and death. We present here whether gene repair activities are associated with neuronal death in an ischemia-reperfusion model that simulates stroke in male Long-Evans rats. This experimental stroke model is known to induce necrosis in the ischemic cortex. Cerebral ischemia causes overactivation of membrane receptors and accumulation of extracellur glutamate and intracellular calcium, which activates neuronal nitric oxide synthase, causing damage to lipids, proteins, and nucleic acids, and reduces energy sources with consequent functional deterioration, leading to cell death. Restoration processes normally repair genes with few errors. However, ischemia elevates oxidative DNA lesions despite these repair mechanisms. These episodes concurrently occur with the induction of immediate-early genes that critically activate other late genes in the signal transduction pathway. Damage, repair, and transcription of the c-FOS gene are presented here as examples, because Fos peptide, one of the components of activator protein 1, activates nerve growth factor and repair mechanisms. The results of our studies show that treatments with 7-nitroindazole, a specific inhibitor of nitric oxide synthase known to attenuate nitric oxide, oxidative DNA lesions, and necrosis, increase intact c-fos mRNA levels after stroke. This suggests that the accuracy of gene expression could be accounted for the recovery of cellular function after cerebral injury.
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PMID:Ischemia-reperfusion-related repair deficit after oxidative stress: implications of faulty transcripts in neuronal sensitivity after brain injury. 1256 81

Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenetic factor of vascular disorders like atherosclerosis and restenosis after angioplasty. In the present study, the possible anti-proliferative effect of a synthetic 1,4-naphthoquinone derivative, 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone (NQ304) was investigated on rat aortic VSMCs. NQ304 was shown to potently inhibit 5% fetal bovine serum (FBS)-induced the growth of VSMCs. Pre-treatment of VSMCs with NQ304 (1-10 microM) for 24 h resulted in significant cell number decreases, i.e., inhibition percentages were 44.75+/-10.77, 73.85+/-6.38 and 89.77+/-6.52% at NQ304 concentrations of 1, 5 and 10 microM, respectively. NQ304 was also found to significantly inhibit 5% FBS-induced DNA synthesis in a concentration-dependent manner. Furthermore, NQ304 elevated p21(cip1) and p27(kip1) mRNA levels and caused G0/G1 phase arrest in cell cycle progression. However, no evidence of NQ304-induced apoptotic or necrotic cell death was obtained, as determined by flow cytometry analysis and DNA fragmentation assays. To investigate the mechanism underlying the anti-proliferative effect of NQ304, we examined the effects of NQ304 on c-fos mRNA expression, activator protein-1 (AP-1) binding activity and extracellular signal-regulated kinase1/2 (ERK1/2) and Akt activation. Pre-treatment of VSMCs with NQ304 (1-10 microM) was found to significantly inhibit the 5% FBS-induced phosphorylations of ERK1/2 and Akt, the activation of AP-1 and the expression of c-fos. These data suggest that the anti-proliferative and cell cycle arresting effects of NQ304 on serum-induced VSMCs may be mediated by AP-1 activation downregulation via the suppression of phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2 signaling pathways, and it may contribute to the prevention of atherosclerosis through inhibition of VSMC proliferation.
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PMID:Potent inhibition of serum-stimulated responses in vascular smooth muscle cell proliferation by 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone, a newly synthesized 1,4-naphthoquinone derivative. 1720 71

Isorhamnetin is one member of flavonoid components which has been used in the treatment of heart disease. Recently the in vitro anti-cancer effect of isorhamnetin on human esophageal squamous carcinoma cell line Eca-109 was investigated in our lab. When Eca-109 cells were in vitro exposed to the graded doses of isorhamnetin (0-80 microg/ml) for 48 h, respectively, isorhamnetin exhibited cytostatic effect on the treated cells, with an IC(50) of 40+/-0.08 microg/ml as estimated by MTT assay. Inhibition on proliferation by isorhamnetin was detected by trypan blue exclusion assay, clone formation test, immunocytochemical assay of PCNA and (3)H-thymidine uptake analysis. Cell cycle distribution was measured by FCM. It was found that the viability of Eca-109 cells was significantly hampered by isorhamnetin. Compared with the negative control group, the treated group which was exposed to isorhamnetin had increased population in G(0)/G(1) phase from 74.6 to 84 while had a significant reduction in G(2)/M phase from 11.9 to 5.8. In addition to its cytostatic effect, isorhamnetin also showed stimulatory effect on apoptosis. Typical apoptotic morphology such as condensation and fragmentation of nuclei and blebbing membrane of the apoptotic cells could be observed through transmission electron microscope. Moreover, the sharp increase in apoptosis rate between the control and treated group were detected by FCM from 6.3 to 16.3. To explore the possible molecular mechanisms that underlie the growth inhibition and apoptosis stimulatory effects of isorhamnetin, the expressions of six proliferation- and death-related genes were detected by FCM. Expressions of bcl-2, c-myc and H-ras were downregulated whereas Bax, c-fos and p53 were upregulated. However, the in vivo experiments were required to further confirm the anti-cancer effects of isorhamnetin. In conclusion, isorhamnetin appears to be a potent drug against esophageal cancer due to its in vitro potential to not only inhibit proliferation but also induce apoptosis of Eca-109 cells.
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PMID:The flavonoid component isorhamnetin in vitro inhibits proliferation and induces apoptosis in Eca-109 cells. 1736 93

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

Excessive intake of fat is a major risk factor for lifestyle-related diseases such as heart disease and also affects brain function such as object recognition memory, social recognition, anxiety behavior, and depression-like behavior. Although oxytocin (OXT) has been reported to improve object recognition, social recognition, anxiety behavior, and depression-like behavior in specific conditions, previous studies did not explore the impact of OXT in high-fat diet (HFD)-fed mice. Furthermore, it remains unclear whether intake of HFD affects OXT/oxytocin receptor (OXTR) in the brain. Here, we demonstrated that peripheral OXT administration improves not only social recognition but also object recognition and depressive-like behavior in HFD-fed mice. In contrast, peripheral OXT administration to HFD-fed male mice increased fear and anxiety-related behavior. In addition, we observed that intake of HFD decreased OXTR and c-fos mRNA expression in the hippocampus, specifically. Furthermore, peripheral OXT administration increased OXT mRNA expression in the hypothalamus. Altogether, these findings suggest that OXT has the potential to improve various recognition memory processes via peripheral administration but also has side effects that increase fear-related behavior in males.
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PMID:Oxytocin Ameliorates Impaired Behaviors of High Fat Diet-Induced Obese Mice. 3271 56