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VEGF contributes to hypoxic vascular remodeling of ovine carotid arteries
Author(s) -
Adeoye Olayemi,
Butler Stacy M,
Semotiuk Andrew M,
Hubbell Margaret C,
Williams James M,
Pearce William J
Publication year - 2011
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.25.1_supplement.1091.13
Subject(s) - adventitia , myosin light chain kinase , hypoxia (environmental) , endocrinology , medicine , myosin , vascular smooth muscle , biology , organ culture , myogenic contraction , anatomy , vasoconstriction , chemistry , microbiology and biotechnology , in vitro , smooth muscle , oxygen , biochemistry , organic chemistry
Hypoxic increases in VEGF are pro‐angiogenic but also may exert important trophic effects on non‐endothelial tissues. To test this hypothesis, endothelium‐denuded common carotid arteries from term fetal and non‐pregnant adult sheep maintained at sea level (FN, AN) or after 110 days at 3820 m (FH, AH) were used to determine active (high K+) stress‐strain relations before organ culture, after 48h of serum starvation, or after 24h starvation + 24h treatment with low physiological concentration (3 ng/ml) of VEGF. Chronic hypoxia increased wall thickness (F: 15%, A: 23%), wall stiffness (F: 13%; A: 24%), smooth muscle alpha actin expression (F: 7%; A: 47%), and regulatory myosin light chain (RLC) expression (F: 89%, A: 82%) and also significantly depressed myogenic tone (F: 74%; A: 40%) and myosin light chain kinase expression (F: 99%; A: 97%). Organ culture with VEGF increased actin expression up to 15% (AH), RLC expression up to 15% (FN & FH) and MLCK up to 133% (FN); all VEGF effects were highly age‐dependent. Importantly, all effects of both hypoxia and VEGF varied significantly among different smooth muscle layers as a function of relative position between the lumen and adventitia, supporting a gradient effect. Together, the results support the hypothesis that VEGF participates in age‐dependent hypoxic vascular remodeling through direct effects on vascular smooth muscle. Supported by PHS grant# PO1‐HD31226