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VEGF mediates age‐dependent remodeling of ovine carotids by chronic hypoxia
Author(s) -
Butler Stacy Michelle,
Abrassart Jenna Marie,
Williams James Michael,
Pearce William Julian
Publication year - 2009
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.23.1_supplement.625.18
Subject(s) - contractility , hypoxia (environmental) , endocrinology , medicine , vascular endothelial growth factor , vascular smooth muscle , extracellular matrix , fetus , artery , biology , chemistry , vegf receptors , microbiology and biotechnology , smooth muscle , organic chemistry , oxygen , pregnancy , genetics
Chronic hypoxia alters arterial structure and contractility through poorly defined mechanisms. Chronic hypoxia also increases expression of the transcription factor HIF that promotes expression of VEGF. This study explores the hypothesis that hypoxic increases in VEGF exert a direct effect on vascular smooth muscle that modulates artery structure and contractility. Carotid arteries from normoxic term fetal (FN), hypoxic (110 days @ 3820 m altitude) term fetal (FH), and hypoxic non‐pregnant adult sheep (SH), were denuded of endothelium and placed in organ culture. After 24 hr serum starvation, segments were treated another 24 hr with vehicle or 30 ng/ml VEGF. Next, stress‐strain relations were determined to functionally define responses to treatment. After VEGF, maximum contractile responses to myogenic stretch and 120 mM K+ were increased in SH, were largely unaffected in FH, and were depressed in FN. Similarly, after VEGF optimal length was increased in SH, was unchanged in FH, and was decreased in FN; the L0 results suggest group specific remodeling of the extracellular matrix. H&E staining confirmed that changes in contractility and L0 were not attributable to cell death. These results support the hypothesis that direct effects of VEGF on vascular smooth muscle contribute to the age‐dependent arterial remodeling associated with chronic hypoxia. Supported by USPHS Grants HL54120, HD31266, & HL64867.