title: Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction.
abstract: OBJECTIVE
  Cardiomyocyte loss is a major contributor to the decreased cardiac function observed in diseased hearts. Previous studies have shown that cardiomyocyte-restricted cyclin D2 expression resulted in sustained cell cycle activity following myocardial injury in transgenic (MHC-cycD2) mice. Here, we investigated the effects of this cell cycle activation on cardiac function following myocardial infarction (MI).
  
  
  RESULTS
  MI was induced in transgenic and non-transgenic mice by left coronary artery occlusion. At 7, 60, and 180 days after MI, left ventricular pressure-volume measurements were recorded and histological analysis was performed. MI had a similar adverse effect on cardiac function in transgenic and non-transgenic mice at 7 days post-injury. No improvement in cardiac function was observed in non-transgenic mice at 60 and 180 days post-MI. In contrast, the transgenic animals exhibited a progressive and marked increase in cardiac function at subsequent time points. Improved cardiac function in the transgenic mice at 60 and 180 days post-MI correlated positively with the presence of newly formed myocardial tissue which was not apparent at 7 days post-MI. Intracellular calcium transient imaging indicated that cardiomyocytes present in the newly formed myocardium participated in a functional syncytium with the remote myocardium.
  
  
  CONCLUSIONS
  These findings indicate that cardiomyocyte cell cycle activation leads to improvement of cardiac function and morphology following MI and may represent an important clinical strategy to promote myocardial regeneration.
authors: Department of Cardiology, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. rjhassink@orange.nl
authors: Rutger J
authors: RJ
authors: Hassink
authors: Kishore B
authors: KB
authors: Pasumarthi
authors: Hidehiro
authors: H
authors: Nakajima
authors: Michael
authors: M
authors: Rubart
authors: Mark H
authors: MH
authors: Soonpaa
authors: Aart Brutel
authors: AB
authors: de la Rivière
authors: Pieter A
authors: PA
authors: Doevendans
authors: Loren J
authors: LJ
authors: Field
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002453:Cell Cycle; D049109:Cell Proliferation; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D011401:Promoter Regions, Genetic; D012038:Regeneration; D013997:Time Factors; D016277:Ventricular Function, Left; D024723:Ventricular Myosins / Q000235:genetics; D017725:Ventricular Pressure
chemical_list: C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains