Pituitary adenylate cyclase-activating polypeptide attenuates tumor necrosis factor-α-induced apoptosis in endothelial colony-forming cells

: Endothelial colony-forming cells (ECFCs) are important in angiogenesis and vascular proliferation. Tumor necrosis factor (TNF)-α is a significant risk factor for the development of atherosclerosis and a key proinflammatory cytokine known to induce apoptosis in endothelial cells. Pituitary adenylate cyclase-activating polypeptide (PACAP) is one of the members of the vasoactive intestinal peptide/secretin/growth hormone-releasing hormone/glucagon superfamily and exists in two biological active forms, PACAP 38 and PACAP 27. PACAP has been reported to help prevent endothelial apoptosis via an anti-inflammatory mechanism. However, to the best of our knowledge, the anti-apoptotic potential of PACAP has not been investigated in ECFCs. The aim of the present study was to demonstrate the efficacy of PACAP for decreasing TNF-α-induced apoptosis in ECFCs. The results indicated that PACAP exerts a cytoprotective effect on ECFCs exposed to TNF-α. Furthermore, PACAP partially rescues the proliferation potential of ECFCs inhibited by prolonged TNF-α exposure. These findings support an anti-inflammatory role for PACAP in circulation diseases.