ABSTRACT
Myocyte loss due to ischemia/reperfusion injury leads to cardiac dysfunction and heart failure, and the concentration of current therapy is limited on preventing the progression. Recent interest has focused on transplantation of stem cells to differentiate and replenish the loss of myocytes. Adipose tissue represents an alternative and abundant source of adult stem cells with the ability to differentiate along multiple lineage pathways. Recent studies have demonstrated the potential of adipose tissue-derived stem cells for treatment of acute myocardial infarction. The aim of this review is to discuss the potential therapeutic benefits of adipose tissue-derived stem cells in improving cardiac function post-injury.
Subject(s)
Adipose Tissue/cytology , Adult Stem Cells/transplantation , Endothelial Cells/pathology , Myocardial Ischemia/surgery , Myocytes, Cardiac/pathology , Regeneration , Stem Cell Transplantation , Adult , Animals , Cell Differentiation , Cell Lineage , Cell Proliferation , Cell Survival , Humans , Myocardial Ischemia/pathology , Myocardial Ischemia/physiopathology , Neovascularization, Physiologic , Treatment OutcomeSubject(s)
Carbolines/pharmacology , Cardiotonic Agents/pharmacology , Imidazoles/pharmacology , Myocardial Infarction/drug therapy , Phosphodiesterase Inhibitors/pharmacology , Piperazines/pharmacology , Sulfones/pharmacology , Animals , Male , Myocardial Ischemia/drug therapy , Myocardial Ischemia/prevention & control , Myocardial Reperfusion Injury/prevention & control , Purines/pharmacology , Rabbits , Rats , Sildenafil Citrate , Species Specificity , Tadalafil , Triazines/pharmacology , Vardenafil DihydrochlorideABSTRACT
We recently demonstrated that monophosphoryl lipid A (MLA)-induced delayed cardioprotection is mediated by inducible nitric oxide synthase (iNOS) in mice. In the present study, we determined whether RC-552, a novel synthetic glycolipid related in chemical structure to MLA, could afford similar protection. Adult mice were pretreated with vehicle or RC-552 (350 microg/kg ip, n = 7 mice/group) 24 h before global ischemia and reperfusion in a Langendorff isolated, perfused heart model. A group of RC-552-treated mice received S-methylisothiourea (SMT), a selective inhibitor of iNOS (3 mg/kg ip), 30 min before heart perfusion. Myocardial infarct size was significantly reduced from 19.2 +/- 2.0% in vehicle to 8.2 +/- 2.9% in RC-552 group (P < 0.05). Treatment with SMT abolished RC-552-induced reduction in infarct size (20.0 +/- 3.9%). In addition, RC-552 failed to reduce infarct size in isolated hearts from iNOS knockout mice (27.1 +/- 2.8%) compared with that in hearts from control knockout mice without drug treatment (22.9 +/- 5.4%). Acute buffer perfusion with RC-552 (0.1, 1.0, or 2.5 microg/ml) for 8 min immediately before ischemia-reperfusion did not reduce infarct size significantly. We concluded that RC-552 induces delayed cardioprotection via an iNOS-dependent pathway.
