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)

Cell-based therapy after myocardial infarction (MI) is a promising therapeutic option but the relevant cell subsets and dosage requirements are poorly defined. We hypothesized that cell therapy for myocardial infarction is improved by ex vivo expansion and high-dose transplantation of defined hematopoietic progenitor cells (HPCs). Since beta-catenin promotes self-renewal of stem cells we evaluated the therapeutic efficacy of beta-catenin-mediated ex vivo expansion of mouse HPCs in a mouse model of myocardial ischemia/reperfusion followed by intraarterial cell delivery. The impact of cell dose was determined by comparing a low-dose (LD, 5 x 10(5) cells) vs. a high-dose (HD, 1 x 10(7) cells) cell transplantation regimen of beta-catenin-HPCs. The impact of beta-catenin modification of HPCs was determined by comparing control-transduced HPCs (GFP-HPCs) vs. transgenic beta-catenin-HPCs. HD beta-catenin-HPCs significantly improved LV function and end-systolic and end-diastolic dimensions as compared to saline and LD beta-catenin-HPCs. Furthermore, while treatment with HD GFP-HPC resulted in a modest cardiac improvement the application of beta-catenin-HPCs was superior, resulting in a significant improvement in EF, FS and LVESD over saline and control GFP-HPC treatment. Although myocardial engraftment of HPCs was only transient, as determined by cell quantification after dye labeling, beta-catenin-HPC treatment significantly decreased infarct size, reduced cardiomyocyte apoptosis and increased capillary angiogenesis in vitro and in vivo. Ex vivo expanded HPCs improve cardiac function and remodeling post MI in a cell number- and beta-catenin-dependent manner.
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PMID:Ex vivo expanded hematopoietic progenitor cells improve cardiac function after myocardial infarction: role of beta-catenin transduction and cell dose. 1867 80

1. The present study was designed to investigate whether the M(3) muscarinic acetylcholine receptors (mAChR) is associated with beta-catenin in the ventricular myocardium during ischaemic myocardial injury and to determine the possible mechanism/s involved. 2. Rat hearts were subjected to coronary artery ligation for 1 and 6 h or 1 month to establish a myocardial ischaemia (MI) model. In the acute MI model, 16 rats were randomized into four groups: (i) control; (ii) ischaemia (rats were subjected to 20 min coronary occlusion); (iii) choline (10 mg/kg, i.v., choline chloride, an M(3) receptor agonist, was administered 15 min before occlusion); and (iv) 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 0.12 mg/kg 4-DAMP, an M(3) receptor antagonist, was administered 20 min before occlusion, followed 5 min later by 10 mg/kg, i.v., choline chloride). Immunochemistry, western blot analysis and immunoprecipitation were used to determine the expression and localization of beta-catenin and the M(3) mAChR. 3. Myocardial ischaemia caused a time-dependent increase in the expression of beta-catenin. Moreover, a physical association was found between beta-catenin and the M(3) mAChR in intercalated discs. This association was enhanced by prolonged ischaemia. Administration of choline before ischaemia not only increased beta-catenin expression, but also strengthened the association between beta-catenin and the M(3) mAChR. However, blockade of M(3) mAChR by 4-DAMP completely inhibited the effect of choline on the expression of beta-catenin. In addition, MI increased phosphorylation of the M(3) mAChR. 4. The results indicate that increased beta-catenin activity is associated with M(3) mAChR during MI. This association is likely to play a role in heart signal transduction during ischaemia between neighbouring ventricular myocardiocum.
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PMID:M3 muscarinic acetylcholine receptor is associated with beta-catenin in ventricular myocytes during myocardial infarction in the rat. 1947 45

(Pro)renin receptor (PRR) contributes to regulating many physiological and pathological processes; however, the role of PRR-mediated signaling pathways in myocardial ischemia/reperfusion injury (IRI) remains unclear. In this study, we used an in vitro model of hypoxia/reoxygenation (H/R) to mimic IRI and carried out PRR knockdown by siRNA and PRR overexpression using cDNA in H9c2 cells. Cell proliferation activity was examined by MTT and Cell Counting Kit-8 (CCK-8) assays. Apoptosis-related factors, autophagy markers and beta-catenin pathway activity were assessed by real-time PCR and western blotting. After 24 h of hypoxia followed by 2 h of reoxygenation, the expression levels of PRR, LC3B-I/II, Beclin1, cleaved caspase-3, cleaved caspase-9 and Bax were upregulated, suggesting that apoptosis and autophagy were increased in H9c2 cells. Contrary to the effects of PRR downregulation, the overexpression of PRR inhibited proliferation, induced apoptosis, increased the expression of pro-apoptotic factors and autophagy markers, and promoted activation of the beta-catenin pathway. Furthermore, all these effects were reversed by treatment with the beta-catenin antagonist DKK-1. Thus, we concluded that PRR activation can trigger H/R-induced apoptosis and autophagy in H9c2 cells through the beta-catenin signaling pathway, which may provide new therapeutic targets for the prevention and treatment of myocardial IRI.
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PMID:(Pro)renin receptor contributes to hypoxia/reoxygenation-induced apoptosis and autophagy in myocardial cells via the beta-catenin signaling pathway. 3246 29