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Overexpression of nitric oxide synthase restores circulating angiogenic cell function in patients with coronary artery disease: Implications for autologous cell therapy for myocardial infarction
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نویسنده
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chen q. ,varga m. ,wang x. ,haddad d.j. ,an s. ,medzikovic l. ,derakhshandeh r. ,kostyushev d.s. ,zhang y. ,clifford b.t. ,luu e. ,danforth o.m. ,rafikov r. ,gong w. ,black s.m. ,suchkov s.v. ,fineman j.r. ,heiss c. ,aschbacher k. ,yeghiazarians y. ,springer m.l.
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منبع
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journal of the american heart association - 2016 - دوره : 5 - شماره : 1
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چکیده
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Background-circulating angiogenic cells (cacs) are peripheral blood cells whose functional capacity inversely correlates with cardiovascular risk and that have therapeutic benefits in animal models of cardiovascular disease. however,donor age and disease state influence the efficacy of autologous cell therapy. we sought to determine whether age or coronary artery disease (cad) impairs the therapeutic potential of cacs for myocardial infarction (mi) and whether the use of ex vivo gene therapy to overexpress endothelial nitric oxide (no) synthase (enos) overcomes these defects. methods and results-we recruited 40 volunteers varying by sex,age (< or =45 years),and cad and subjected their cacs to well-established functional tests. age and cad were associated with reduced cac intrinsic migration (but not specific response to vascular endothelial growth factor,adherence of cacs to endothelial tubes,enos mrna and protein levels,and no production. to determine how cac function influences therapeutic potential,we injected the 2 most functional and the 2 least functional cac isolates into mouse hearts post mi. the high-function isolates substantially improved cardiac function,whereas the low-function isolates led to cardiac function only slightly better than vehicle control. transduction of the worst isolate with enos cdna adenovirus increased no production,migration,and cardiac function of post-mi mice implanted with the cacs. transduction of the best isolate with enos small interfering rna adenovirus reduced all of these capabilities. conclusions-age and cad impair multiple functions of cacs and limit therapeutic potential for the treatment of mi. enos gene therapy in cacs from older donors or those with cad has the potential to improve autologous cell therapy outcomes. © 2016 the authors.
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کلیدواژه
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Circulating angiogenic cells; Endothelial progenitor cells; Gene therapy; Myocardial infarction; Nitric oxide synthase
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آدرس
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cardiovascular research institute,university of california,san francisco,san francisco,ca, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca,united states,silk road medical,sunnyvale,ca, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca,united states,university of vermont college of medicine,burlington,vt, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca, United States, department of pediatrics,university of california,san francisco,san francisco,ca,united states,academic medical center,amsterdam, Netherlands, department of pediatrics,university of california,san francisco,san francisco,ca, United States, department of pediatrics,university of california,san francisco,san francisco,ca,united states,i.m. sechenov the first moscow state medical university,moscow, Russian Federation, department of pediatrics,university of california,san francisco,san francisco,ca,united states,silver creek pharmaceuticals,san francisco,ca, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca,united states,scripps clinic,la jolla,ca, United States, department of pediatrics,university of california,san francisco,san francisco,ca, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca,united states,rush medical college,chicago,il, United States, eli and edythe broad institute of regeneration medicine and stem cell research,university of california,san francisco,san francisco,ca, United States, department of pediatrics,university of california,san francisco,san francisco,ca, United States, eli and edythe broad institute of regeneration medicine and stem cell research,university of california,san francisco,san francisco,ca, United States, department of medicine,university of arizona,tucson,az,united states,i.m. sechenov the first moscow state medical university,moscow, Russian Federation, cardiovascular research institute,university of california,san francisco,san francisco,ca, United States, department of pediatrics,university of california,san francisco,san francisco,ca,united states,division of cardiology,pulmonary and vascular medicine,medical faculty,university duesseldorf,duesseldorf, Germany, division of cardiology,university of california,san francisco,san francisco,ca, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca,united states,department of pediatrics,university of california,san francisco,san francisco,ca,united states,department of psychiatry,university of california,san francisco,san francisco,ca, United States, cardiovascular research institute,university of california,san francisco,san francisco,ca,united states,department of pediatrics,university of california,san francisco,san francisco,ca,united states,department of psychiatry,university of california,san francisco,san francisco,ca, United States
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Authors
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