TRAIL promotes the survival and proliferation of primary human vascular endothelial cells by activating the Akt and ERK pathways

Article

关键词: TUMOR-NECROSIS-FACTOR;    NF-KAPPA-B;    FAS-MEDIATED APOPTOSIS;    SMOOTH-MUSCLE;    LIGAND;    KINASES;    DEATH;    ANGIOGENESIS;    EXPRESSION;    MECHANISMS;   

DOI  :  10.1161/01.CIR.0000062702.60708.C4

来源: SCIE

【 摘 要 】

Background - TRAIL protein is expressed in the medial smooth cell layer of aorta and pulmonary artery, whereas endothelial cells express all TRAIL receptors ( TRAIL-Rs). Methods and Results - The role of TRAIL/TRAIL-Rs in vascular biology was investigated in primary human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells, which showed comparable surface expression of death (TRAIL-R1 and - R2) and decoy (TRAIL-R3 and - R4) TRAIL-Rs. TRAIL activated the protein kinase Akt in HUVECs, as assessed by Western blot for phospho-Akt. Moreover, experiments performed with a pharmacological inhibitor of the phosphatidylinositol 3-kinase/Akt pathway (LY294002) or a dominant-negative Akt (K179M) demonstrated that TRAIL significantly protected HUVECs from apoptosis induced by trophic withdrawal via Akt and that inhibition of Akt sensitized HUVECs to TRAIL-induced caspase-dependent apoptosis. TRAIL also stimulated the ERK1/2 but not the p38 or the JNK pathways and induced a significant increase in endothelial cell proliferation in an ERK-dependent manner. Conversely, TRAIL did not activate NF-kappaB or affect the surface expression of the inflammatory markers E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Conclusions - The ability of TRAIL to promote the survival/proliferation of endothelial cells without inducing NF-kappaB activation and inflammatory markers suggests that the TRAIL/TRAIL-R system plays an important role in endothelial cell physiology.

【 授权许可】

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