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Differential pAkt activation by VEGF splice variant proteins VEGF 120 and VEGF 205 * in endothelial cells during wound healing in‐vitro : impact of NOS3 Glu298Asp genotype
Author(s) -
Joshi Mandar S,
Schanbacher Brandon L,
Affara Nesrine I,
Robertson Fredika M,
Bauer John Anthony
Publication year - 2006
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.20.4.a719
Subject(s) - wound healing , vascular endothelial growth factor , in vitro , umbilical vein , microbiology and biotechnology , biology , chemistry , vegf receptors , endocrinology , immunology , cancer research , genetics
Vascular Endothelial Growth Factor (VEGF) proteins are key growth factors that regulate endothelial responses via effects on endothelial nitric oxide synthase (NOS3), but the mechanisms and genetic predispositions are not well defined. We tested the hypothesis that VEGF proteins have distinct actions on human umbilical vein endothelial cells (ECs) in‐vitro . We evaluated EC functional responses after exposure to VEGF splice variants VEGF 120 & VEGF 205 * by measuring EC wound healing responses in‐vitro . VEGF 205 * treated ECs had significantly enhanced wound closure after 48h as compared to VEGF 120 (54.41±2.04 vs. 26.92±3.41; VEGF 205* vs. VEGF 120 : p<0.05). We also investigated the levels of nuclear activated Akt (pAkT) following exposure to VEGF splice variants. VEGF205* exposed ECs had enhanced levels of nuclear pAkt as compared to VEGF 120 exposed ECs. Moreover, VEGF 205* dependent wound healing was associated with increased pAkt levels in ECs. In addition the NOS3 exon7 Glu298Asp variant genotypes contained a diminished level of nuclear pAkt activation in response to VEGF 205* . These studies demonstrate that VEGF splice variant proteins elicit specific functional responses in ECs and demonstrate a role for the NOS3 Glu298Asp SNP with respect to VEGF actions. Our findings also support a role for nuclear pAkt activation in ECs for regulation of EC wound closure and illustrate important functional differences between two protein products derived from the same VEGF gene.