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)

Cardiotrophin-1 (CT-1), a novel cytokine that belongs to the interleukin-6 cytokine family, activates gp130 dependent signaling pathway to transduce hypertrophic and cytoprotective signals in cardiac myocytes. To investigate the pathophysiological significance of CT-1 in myocardial disease, the expression of CT-1 was examined after hypoxic stimulation in cardiac myocytes. Highly expressed CT-1 mRNA was observed in embryonic and adult hearts by RNase protection assay. Cardiac myocytes subjected to hypoxic stimulation augmented CT-1 mRNA expression. Although CT-1 mRNA was expressed to a higher extent in non-myocardial cells, the expression was not affected with the stimulation. Conditioned medium from cultured cardiac myocytes presented the ability to tyrosine phosphorylate STAT3 through gp130 and that was further augmented with hypoxic conditioned medium. These results demonstrated for the first time that CT-1 expression is augmented after hypoxic stimulation and hypoxic conditioned medium presented enhanced ability to activate STAT3 in cardiac myocytes. CT-1 might play an important role in the pathogenesis of ischemic heart disease.
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PMID:Hypoxic stress induces cardiotrophin-1 expression in cardiac myocytes. 1052 82

Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been shown to be elevated in the serum of patients with ischemic heart disease and valvular heart disease, and induces cardiomyocyte hypertrophy in vitro. We investigated expression of CT-1 in post-MI rat heart and the effect of CT-1 on cultured primary adult rat cardiac fibroblasts. Elevated CT-1 expression was observed in the infarct zone at 24 h and continued through 2, 4 and 8 weeks post-MI, compared to sham-operated animals. CT-1 induced rapid phosphorylation of Jak, Jak2, STAT1, STAT3, p42/44 MAPK and Akt in cultured adult cardiac fibroblasts. CT-1 induced cardiac fibroblast protein synthesis and proliferation. Protein and DNA synthesis were dependent on activation of Jak/STAT, MEK1/2, PI3K and Src pathways as evidenced by decreased 3H-leucine and 3H-thymidine incorporation after pretreatment with AG490, PD98059, LY294002 and genistein respectively. Furthermore, CT-1 treatment increased procollagen-1-carboxypropeptide (PICP) synthesis, a marker of mature collagen synthesis. CT-1 induced cell migration of rat cardiac fibroblasts. Our results suggest that CT-1, as expressed in post-MI heart, may play an important role in infarct scar formation and ongoing remodeling of the scar. CT-1 was able to initiate each of the processes considered important in the formation of infarct scar including cardiac fibroblast migration as well as fibroblast proliferation and collagen synthesis. Further work is required to determine factors that induce CT-1 expression and interplay with other mediators of cardiac infarct wound healing in the setting of acute cardiac ischemia and chronic post-MI heart failure.
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PMID:Cardiotrophin-1: expression in experimental myocardial infarction and potential role in post-MI wound healing. 1467 4

Ischemic heart disease is the most common cause of mortality worldwide. Cardiac fibroblasts and myofibroblasts, i.e., the hypersecretory, muscular, and contractile fibroblastic phenotype variant, play an important role in myocardial healing and are responsible for accumulation of collagen in the infarct scar as well as in viable myocardium. Thus, cardiac fibroblasts and myofibroblasts directly contribute to cardiac stiffness, altered performance, and ultimately to the onset of systolic and diastolic heart failure. Cardiotrophin-1 (CT-1) is a member of the IL-6 superfamily and is elevated in the serum of patients with ischemic heart disease and valvular heart disease; it is also known to induce cardiomyocyte hypertrophy in vitro. The recent, burgeoning awareness of the functions of IL-6 superfamily of cytokines within cardiovascular diseases predicates this summary of CT-1's effect in cardiac wound healing, and particularly after the induction of myocardial infarction. Further, we summarize recent results of cardiac CT-1 expression post-myocardial infarction (post-MI) as well as the effect of CT-1 on cultured primary adult rat cardiac fibroblasts with respect to proliferation and collagen secretion. It would appear that CT-1 plays an important and heretofore largely unrecognized role in infarct scar formation and angiogenesis in the rat model of chronic MI. Further work is required to determine factors that induce CT-1 expression, its interplay with other mediators of cardiac infarct wound healing in the setting of acute cardiac ischemia and chronic post-MI heart failure, and ultimately whether it confers a beneficial effect or contributes to maladaptive cardiac fibrosis.
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PMID:Emerging evidence for the role of cardiotrophin-1 in cardiac repair in the infarcted heart. 1572 58

Cardiac ischemia-reperfusion alters sympathetic neurotransmission in the heart, but little is known about its effect on neuropeptide expression in sympathetic neurons. Ischemia followed by reperfusion induces the production of inflammatory cytokines in the heart, including interleukin-6 and cardiotrophin-1. These cytokines and related molecules inhibit the expression of neuropeptide Y (NPY), and stimulate the expression of vasoactive intestinal peptide (VIP), substance P (SubP), and galanin (GAL) in cultured sympathetic neurons. Therefore, we quantified NPY, VIP, SubP, and GAL mRNA in neurons of the stellate ganglia 1 week after ischemia-reperfusion to determine if neuropeptide expression was altered in cardiac sympathetic neurons. NPY, VIP, and SubP mRNAs were unchanged compared to unoperated control animals, but GAL mRNA was increased significantly. The increased GAL mRNA was not accompanied by elevated GAL peptide content in the stellate ganglia. Galanin content was increased significantly in the heart, however, indicating that elevated GAL mRNA led to increased peptide production. GAL content was increased in the left ventricle below the coronary artery ligation, but was not increased significantly in the atria or the base of the heart above the ligation. The buildup of GAL specifically in the damaged left ventricle is consistent with previous reports that GAL is transported to regenerating nerve endings after axon damage.
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PMID:Myocardial infarction stimulates galanin expression in cardiac sympathetic neurons. 1575 42