Chronic Akt1 deficiency attenuates adverse remodeling and enhances angiogenesis after myocardial infarction

K. Vandoorne, M.H. Vandsburger, T. Raz, M. Shalev, K. Weisinger, I. Biton, V. Brumfeld, C. Raanan, N. Nevo, R. Eilam, B.A. Hemmings, E. Tzahor, A. Harmelin, L. Gepstein, M. Neeman

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    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. Methods and 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.
    Original languageEnglish
    Pages (from-to)992-1000
    Number of pages9
    JournalCirculation. Cardiovascular Imaging
    Volume6
    Issue number6
    DOIs
    Publication statusPublished - 2013

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