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A Genetic Approach to Defining the Role of Glucose in Vascular Remodeling
Author(s) -
Adhikari Neeta,
Mariash Ami,
Basi David,
McCue Jonathan,
Heilig Charles,
Hall Jennifer
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.a637
Subject(s) - glut1 , glucose transporter , medicine , glucose uptake , matrix metalloproteinase , endocrinology , vascular smooth muscle , glucose transporter type 1 , insulin , aorta , transgene , lesion , biology , chemistry , biochemistry , gene , smooth muscle , pathology
The contributing role of glucose in vascular disease is controversial. The goal of this study was to use a genetic approach to test the hypothesis that increasing cellular glucose uptake was sufficient to alter vascular remodeling in response to injury. Two transgenic models were established harboring the insulin‐independent glucose transporter (Glut1) under the control of the smooth muscle specific sm22alpha promoter (Sm22Glut1) and the ubiquitous beta‐actin promoter (beta‐actinGlut1). Glut1 protein in the aorta and glucose uptake in isolated aortic smooth muscle cells were significantly increased in both models (sm22Glut1 5183±141 cpm, beta‐actinGlut1 8289±367 cpm, wild type 2059±239 cpm, p<0.05, n=3). Fasting blood glucose, non‐esterified fatty acids, and insulin levels were unaffected. Up‐regulation of Glut1 led to an increase in circulating matrix metalloproteinase‐9 (MMP‐9) (sm22Glut1 236±55 ng/mL, beta‐actinGlut1 641±89 ng/mL, wild type 85±10 ng/mL, n=4‐6, p<0.05). Vascular injury induced a marked increase in local MMP‐9 expression in the lesion of both models along with a significant increase in the number of macrophages and a decrease in smooth muscle cells. In summary, the data suggest that increased cellular glucose uptake elevates circulating and local MMP‐9 and promotes an inflammatory phenotype in the vessel. This study was supported by funding from the Lillehei Heart Institute.