In vivo bioluminescence imaging of inducible nitric oxide synthase gene expression in vascular inflammation.
OBJECTIVE
Inflammation plays a critical role in atherosclerosis and is associated with upregulation of inducible nitric oxide synthase (iNOS). We studied bioluminescence imaging (BLI) to track iNOS gene expression in a murine model of vascular inflammation.


METHODS
Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in 18 iNOS-luc reporter mice. In vivo iNOS expression was imaged serially by BLI over 14 days, followed by in situ BLI and histology.


RESULTS
BLI signal from ligated carotids increased over 14 days (9.7 ± 4.4 × 10(3 ) vs. 4.4 ± 1.7 × 10(3) photons/s/cm(2)/sr at baseline, p < 0.001 vs. baseline, p < 0.05 vs. sham controls). Histology confirmed substantial macrophage infiltration, with iNOS and luciferase expression, only in ligated left carotid arteries and not controls.


CONCLUSIONS
BLI allows in vivo detection of iNOS expression in murine carotid lesions and may provide a valuable approach for monitoring vascular gene expression and inflammation in small animal models.
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305-5233, USA.
Masahiro
M
Terashima
Shoichi
S
Ehara
Eugene
E
Yang
Hisanori
H
Kosuge
Philip S
PS
Tsao
Thomas
T
Quertermous
Christopher H
CH
Contag
Michael V
MV
McConnell
D000818:Animals; D017536:Carotid Artery, Common / Q000201:enzymology / Q000473:pathology*; D015971:Gene Expression Regulation, Enzymologic; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics*; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D008264:Macrophages; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D013194:Staining and Labeling
D008156:Luciferases; D052247:Nitric Oxide Synthase Type II