Extending cardiomyocyte replicative capacity into adulthood improves outcomes after myocardial injury but repair is incomplete
作者单位：Cardiac Regeneration Research InstituteWenzhou Medical University Division of Molecular Cardiology and BiophysicsVictor Chang Cardiac Research Institute St Vincent’s Clinical SchoolUniversity of New South Wales Department of MedicineEmory University School of Medicine
会议日期：2016年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：Cardiac regeneration cardiomyocyte proliferation myocardial infarct
摘 要：Aims:We have previously demonstrated that cardiomyocytes(CMs) of adult transgenic C57 BL/6 J mice with CM-restricted overexpression of the dominant negative Wv mutant(dn-c-kit-Tg) retain the ability to proliferate;a response normally restricted to fetal and early neonatal *** leads to a hyperplastic CM response to pressure overload with improved cardiac function and ***,we tested if this persistent CM proliferative competence allows complete,scar-less repair of the myocardium with normalization of cardiac morphology and function post-myocardial infarction(MI).Methods and *** to WT control non-transgenic littermates,dn-c-kit-Tg mice displayed i) persistent CM replicative capacity in adulthood,ii) a thicker left ventricular(LV) wall and a smaller LV cavity due to increased CM cell number,but no change in CM length,width,volume,pbidy or nucleation state,and iii) improved *** 24 hours after ligation of the left anterior descending coronary artery,infarct sizes were similar in adult(16 week old) WT and dn-c-kit-Tg *** weeks post-MI,infarct size in dn-c-kk-Tg was half that in WT hearts,but significant scarring was still *** infarct size in the dn-c-kit-Tg mice was associated with improved survival,increased CM cell cycle entry,attenuated left ventricular remodelling and improved cardiac ***:Extending CM replicative capacity into adulthood improves outcomes post-MI,but healing is structurally and functionally incomplete.