Akt1 in the cardiovascular system: friend or foe?
J. Clin. Invest. Brian T. O’Neill, et al. 115:2059 doi:10.1172/JCI25900 [
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Figure 2Akt1 promotes adaptive angiogenesis. In endothelial cells and VSMCs, Akt1 represents the predominant isoform. VEGF-mediated angiogenesis requires Akt1 activation. Angiogenesis is mediated in part by Akt1-dependent activation of eNOS, which leads to increased NO production. VEGF also phosphorylates glycogen synthase kinase_3β (GSK3β) and FOXO1, both of which may also contribute to Akt1-dependent angiogenesis. Akt1 is also required for the recruitment of bone marrow_derived endothelial precursor cells to sites of ischemia and for the migration of mature endothelial cells and fibroblasts to areas of active new vessel formation. Note that although Akt2 is expressed in fibroblasts, its expression is not required for promoting fibroblast migration. Akt1-mediated cross-talk between endothelium and cardiomyocyte involves the release of VEGF from cardiomyocytes, which may influence the vascular response to hypertrophy. It is also likely that Akt1-mediated release of NO from the vasculature will have important regulatory effects on the cardiomyocyte.
