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EARLY MICROVESSEL LOSS IN THE METABOLIC SYNDROME
Author(s) -
Goodwill Adam G.,
Butcher Joshua,
Brock Robert,
Olfert I. Mark,
Frisbee Jefferson C
Publication year - 2012
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.26.1_supplement.682.9
Subject(s) - microvessel , medicine , inflammation , metabolic syndrome , rarefaction (ecology) , endocrinology , insulin resistance , diabetes mellitus , biology , angiogenesis , ecology , species diversity
The metabolic syndrome (MS) is an integrated disorder reflecting development of multiple risk factors for a poor cardiovascular outcome, including obesity, insulin resistance and genesis of pro‐inflammatory/ pro‐oxidant environment. The obese Zucker rat (OZR) represents an excellent model of MS, with impairments to vascular reactivity due to low NO bioavailability and altered arachidonic acid metabolism and a parallel reduction to skeletal muscle microvessel density (MVD, rarefaction); key contributors to poor perfusion outcomes. While the full extent of rarefaction is well predicted by the loss of NO, we have determined that an early pulse of rarefaction develops in OZR which precedes any loss in NO bioavailability, and without which the NO‐dependent loss in MVD is attenuated. Subsequent experiments suggest that the strongest predictors of early rarefaction are shifts in vascular inflammation (TNF‐α), increased production of thromboxane A 2 (TxA 2 ) and venular leukocyte adhesion. Current experiments have supported this conceptual model, as targeted interventions have abolished the early rarefaction, with initial candidate proteomic targets being the ratio of thrombospondin‐1 (TSP‐1)/VEGF, MCP‐1 and s‐ICAM. Future experiments will determine if prevention of venular leukocyte adhesion represents an effective target to blunt rarefaction (NIH RR2465AR; T32 HL90610, AHA 0740129N; AHA PRE3040016)