Transplantation of mesenchymal stem cells （MSCs） for myocardial reconstruction has shown promise in both animal models and human phase 1 clinical studies. Vascular endothelial growth factor （VEGF） is a strong ther...Transplantation of mesenchymal stem cells （MSCs） for myocardial reconstruction has shown promise in both animal models and human phase 1 clinical studies. Vascular endothelial growth factor （VEGF） is a strong therapeutic agent for treating ischaemia by inducing angiogenesis. The feasibility of ex vivo MSCs mediated gene transfer is documented. Matsumoto and colleagues have recently reported genetically engineered MSCs carrying VEGF165 delivery for revascularization in a model of acute myocardial infarction （MI）. The promising data from our laboratory in both angiogenesis and MSCs transplantation in cunicular heart model of acute MI have prompted us to attempt the combined and simultaneous application of the two strategies.展开更多
Background Nitric oxide （NO） is a biologically active molecule which has been reported to protect the heart against ischemia and reperfusion injury in different species. This study aimed to test the hypothesis that ...Background Nitric oxide （NO） is a biologically active molecule which has been reported to protect the heart against ischemia and reperfusion injury in different species. This study aimed to test the hypothesis that nitric oxide may induce the expression of heat shock protein 72 （HSP72） which may protect the heart against ischemia.Methods Rabbits were given intravenous saline or S-nitroso-N-acetylpenicillamine （SNAP）, a nitric oxide donor, or Zaprinast, an inhibitor of cyclic guanosine monophosphate （GMP）-phosphodiesterase, which may increase myocardial cyclic GMP content. Twenty-four hours later, the rabbits were either sampled to measure HSP72, or induced with a 30-minute coronary occlusion followed by a 120-minute reperfusion, and then the infarct size was measured. Meanwhile, chelerythrine （CHE, an inhibitor of protein kinase C） was given intravenously 5 minutes before SNAP injection and the effect on HSP72 expression and infarct size was determined.Results Twenty-four hours after pretreatment, immunoblotting showed HSP72 expression increased in the SNAP group compared with control groups, and this was blocked by CHE. Myocardial infarct size in the SNAP group was smaller than that of the control group （（32.4±5.8）% vs （51.1±4.7）%, P 〈0.05）. Pretreated with CHE abolished the infarct size-limiting effect of SNAP （（46.0±5.1）%）. Pretreatment with Zaprinast neither induced HSP72 expression nor reduced infarct size （（55.4±5.4）%）.Conclusion NO induced HSP72 expression and a delayed protection to the heart via the activities of protein kinase C by a cyclic GMP-independent pathway.展开更多
基金This work was supported in part by grants from the National Nature Science Foundation of China (No. 30471923 and No. 30570667) and Shaanxi Provincial Science Grant (No. 2004C2-03).
文摘Transplantation of mesenchymal stem cells （MSCs） for myocardial reconstruction has shown promise in both animal models and human phase 1 clinical studies. Vascular endothelial growth factor （VEGF） is a strong therapeutic agent for treating ischaemia by inducing angiogenesis. The feasibility of ex vivo MSCs mediated gene transfer is documented. Matsumoto and colleagues have recently reported genetically engineered MSCs carrying VEGF165 delivery for revascularization in a model of acute myocardial infarction （MI）. The promising data from our laboratory in both angiogenesis and MSCs transplantation in cunicular heart model of acute MI have prompted us to attempt the combined and simultaneous application of the two strategies.
文摘Background Nitric oxide （NO） is a biologically active molecule which has been reported to protect the heart against ischemia and reperfusion injury in different species. This study aimed to test the hypothesis that nitric oxide may induce the expression of heat shock protein 72 （HSP72） which may protect the heart against ischemia.Methods Rabbits were given intravenous saline or S-nitroso-N-acetylpenicillamine （SNAP）, a nitric oxide donor, or Zaprinast, an inhibitor of cyclic guanosine monophosphate （GMP）-phosphodiesterase, which may increase myocardial cyclic GMP content. Twenty-four hours later, the rabbits were either sampled to measure HSP72, or induced with a 30-minute coronary occlusion followed by a 120-minute reperfusion, and then the infarct size was measured. Meanwhile, chelerythrine （CHE, an inhibitor of protein kinase C） was given intravenously 5 minutes before SNAP injection and the effect on HSP72 expression and infarct size was determined.Results Twenty-four hours after pretreatment, immunoblotting showed HSP72 expression increased in the SNAP group compared with control groups, and this was blocked by CHE. Myocardial infarct size in the SNAP group was smaller than that of the control group （（32.4±5.8）% vs （51.1±4.7）%, P 〈0.05）. Pretreated with CHE abolished the infarct size-limiting effect of SNAP （（46.0±5.1）%）. Pretreatment with Zaprinast neither induced HSP72 expression nor reduced infarct size （（55.4±5.4）%）.Conclusion NO induced HSP72 expression and a delayed protection to the heart via the activities of protein kinase C by a cyclic GMP-independent pathway.
