Abstract:

-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 multi-modal in vivo imaging to investigate the impact of systemic Akt1 deficiency on cardiac function and angiogenesis before and after MI. -In vivo cardiac magnetic resonance imaging (MRI) was performed before and at day 1, 8, 15 and 29-30 after MI induction for wildtype, heterozygous, and Akt1 deficient mice. Non-infarcted hearts were imaged using ex vivo stereomicroscopy and μCT. Histological examination was performed for non-infarcted hearts and for hearts at days 8 and 29-30 post-MI. MRI revealed mildly decreased baseline cardiac function in Akt1 null mice, while ex vivo stereomicroscopy and μCT 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, were observed in Akt1(-/-) mice when compared to littermate controls. -Using multi-modal 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.