Significance of vascular hormones in vasculoangiogenesis and vascular endocrinological approach to organ protection and regeneration

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We previously demonstrated that vascular hormones secreted from endothelial cells not only regulate vascular tone but also vascular remodeling, and also reported that Flk-1, one of VEGF receptors, -positive cells derived from ES cells can be differentiated into endothelial cells and vascular smooth muscle cells (VSMC) to construct blood vessels in vitro and named them as "vascular progenitor cells (VPC)". In this research, by using several genetically-engineered mice, we revealed that activation of natriuretic peptides/cGMP/cGMP-dependent protein kinase (cGK) pathway accelerates endothelial repair to recover endothelial functions and induces vascular regeneration. Natriuretic peptides inhibit Rho activity by directly phosphorylating Ser residue of Rho in (VSMC) and activate Erk 1/2 and Akt in endothelial cells. Gene transfer of CNP, which we elucidated to act as endothelium-derived relaxing peptide, potentiated blood in hind limb-ischemia model. Implasntation of ES cell-derived VPC differentiated by VEGF into adult mice resulted in neo vessel formation to augment local blood flow.