title: Chronic Akt1 deficiency attenuates adverse remodeling and enhances angiogenesis after myocardial infarction.
abstract: BACKGROUND
  Akt1 is a key signaling molecule in multiple cell types, including endothelial cells. Accordingly, Akt1 was proposed as a therapeutic target for ischemic injury in the context of myocardial infarction (MI). The aim of this study was to use multimodal in vivo imaging to investigate the impact of systemic Akt1 deficiency on cardiac function and angiogenesis before and after MI.
  
  
  RESULTS
  In vivo cardiac MRI was performed before and at days 1, 8, 15, and 29 to 30 after MI induction for wild-type, heterozygous, and Akt1-deficient mice. Noninfarcted hearts were imaged using ex vivo stereomicroscopy and microcomputed tomography. Histological examination was performed for noninfarcted hearts and for hearts at days 8 and 29 to 30 after MI. MRI revealed mildly decreased baseline cardiac function in Akt1 null mice, whereas ex vivo stereomicroscopy and microcomputed tomography revealed substantially reduced coronary macrovasculature. After MI, Akt1(-/-) mice demonstrated significantly attenuated ventricular remodeling and a smaller decrease in ejection fraction. At 8 days after MI, a larger functional capillary network at the remote and border zone, accompanied by reduced scar extension, preserved cardiac function, and enhanced border zone wall thickening, was observed in Akt1(-/-) mice when compared with littermate controls.
  
  
  CONCLUSIONS
  Using multimodal imaging to probe the role of Akt1 in cardiac function and remodeling after MI, this study revealed reduced adverse remodeling in Akt1-deficient mice after MI. Augmented myocardial angiogenesis coupled with a more functional myocardial capillary network may facilitate revascularization and therefore be responsible for preservation of infarcted myocardium.
authors.affiliation: Department of Biological Regulation.
authors.forename: Katrien
authors.initials: K
authors.lastname: Vandoorne
authors.forename: Moriel H
authors.initials: MH
authors.lastname: Vandsburger
authors.forename: Tal
authors.initials: T
authors.lastname: Raz
authors.forename: Moran
authors.initials: M
authors.lastname: Shalev
authors.forename: Karen
authors.initials: K
authors.lastname: Weisinger
authors.forename: Inbal
authors.initials: I
authors.lastname: Biton
authors.forename: Vlad
authors.initials: V
authors.lastname: Brumfeld
authors.forename: Calanit
authors.initials: C
authors.lastname: Raanan
authors.forename: Nava
authors.initials: N
authors.lastname: Nevo
authors.forename: Raya
authors.initials: R
authors.lastname: Eilam
authors.forename: Brian A
authors.initials: BA
authors.lastname: Hemmings
authors.forename: Eldad
authors.initials: E
authors.lastname: Tzahor
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.forename: Lior
authors.initials: L
authors.lastname: Gepstein
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency* / Q000378:metabolism; D020257:Ventricular Remodeling; D055114:X-Ray Microtomography
chemical_list: C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt1 protein, mouse; angiogenesis, pathologic; heart; myocardial infarction