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Development of a predictive model for negative microvascular outcomes in the metabolic syndrome
Author(s) -
Frisbee Jefferson C.,
Goodwill Adam G.,
James Milinda E.,
Brock Robert W.,
Hollander John M.,
Frisbee Stephanie J.
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.594.11
Subject(s) - metabolic syndrome , medicine , insulin resistance , endothelial dysfunction , endocrinology , physiology , diabetes mellitus , insulin
Evolution of the metabolic syndrome is a multi‐factorial process with a constellation of pathologies developing over time. Consequently, poor vascular outcomes in the metabolic syndrome are also temporally distributed, and an integrated understanding of these outcomes requires information regarding their sequence of development. To address this, we examined development of the metabolic syndrome, systemic disease biomarkers, and negative vascular structural/functional outcomes in obese Zucker rats at 6‐7, 9‐10, 12‐13, 15‐16 and 19‐20 weeks. For these initial procedures and model development, no interventional strategy against either the metabolic syndrome or the poor outcomes was employed. Prior to development of vascular dysfunction, endothelial arachidonic acid metabolism was altered toward TxA 2 production; predicted by insulin resistance. This outcome was followed by an increase in markers of systemic inflammation, resulting in systemic oxidant stress and reduced vascular NO bioavailability. Immunohistochemistry suggested an increased venular adhesion marker expression (ICAM‐1, VCAM‐1) associated with the loss of NO bioavailability and this contributed significantly to a reduction in microvessel density. Taken together, these data begin to provide a temporally relevant, predictive model for poor microvascular outcomes in the metabolic syndrome. (NIH R01 DK64668, AHA EIA 0740129N)