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The role of the VEGF/eNOS signaling pathway in cardiovascular development: a novel target to advance cardiovascular regeneration (1078.11)
Author(s) -
Gentile Carmine,
Remedios Cristobal,
Drake Christopher,
Davies Michael
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1078.11
Subject(s) - enos , umbilical vein , microbiology and biotechnology , biology , signal transduction , s nitrosylation , vascular endothelial growth factor , nitric oxide , cancer research , endocrinology , nitric oxide synthase , in vitro , vegf receptors , biochemistry , cysteine , enzyme
In vivo and in vitro models of murine and human endothelial cells (ECs) and cardiomyocytes (CMs) have been used to study the emerging roles played by the vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway in cardiovascular development. In vivo studies using mouse embryos showed that eNOS is first expressed by Flk‐1 (VEGF receptor 2)‐positive ECs of the endocardium earlier than in CMs. In vivo studies also showed that this occurs as early as at 8 days post‐coitum in mice, a developmental stage when both ECs and CMs are proliferating. Our in vitro studies using human umbilical vein endothelial cells (HUVECs) identified cyclin B1 as a novel molecular target of the VEGF/eNOS signaling pathway controlling EC proliferation. VEGF/eNOS‐mediated S‐nitrosylation of cyclin B1 in HUVECs occurs following formation of the “signalosome”, the multimolecular complex responsible for the S‐nitrosylation of several target proteins via HSP90. Pharmacological inhibition of HSP90 using 17‐AAG reduced the VEGF/eNOS‐mediated proliferative effects on human ECs. Taken together, our studies showed that the VEGF/eNOS signaling pathway via S‐nitrosylation of cyclin B1 represents a novel molecular target for cardiovascular regeneration in patients with cardiovascular disease. Current studies are focused on establishing the role of the VEGF/eNOS signaling pathway in CM development. Grant Funding Source : Supported by Marcus Blackmores Fellowship and the Translational‐in‐Aid‐Grant (Bosch Institute)