Vascular inflammation in absence of blood pressure elevation in transgenic murine model overexpressing endothelin-1 in endothelial cells.
OBJECTIVE
We previously showed that in transgenic mice with endothelium-targeted overexpression of human preproendothelin-1, mesenteric resistance arteries exhibited vascular remodeling, endothelial dysfunction and increased oxidative stress early in life in the absence of significant elevation of blood pressure. To further characterize this model, the role of vascular inflammation was investigated in young male transgenic and wild-type littermate mice.


RESULTS
Systemic and local inflammatory markers in mesenteric arteries were assessed by Luminex-based enzyme-linked immunosorbent assay technique, confocal microscopy, electrophoretic mobility shift assay and western blotting in 10-week old male transgenic and wild-type mice. Although no differences were found for systemic inflammatory markers, vascular staining for monocyte chemoattractant protein-1 and macrophage infiltration were significantly increased (P < 0.05) in transgenic mice compared with wild-type littermates. Transgenic mice exhibited significant increase (P < 0.01) in the activation of transcription factors activator protein-1 and nuclear factor kappa B compared with wild-type littermates. Western blotting analysis showed significantly increased (P < 0.05) blood vessel wall expression of vascular cell adhesion molecule-1 in transgenic mice.


CONCLUSIONS
These findings suggest that in this murine model of endothelial cell-restricted preproendothelin-1 overexpression, endothelin-1 induces vascular inflammation by multiple pathways in young animals in the absence of blood pressure elevation or systemic inflammation.
Amiri
Farhad
F
Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Paradis
Pierre
P
Reudelhuber
Timothy L
TL
Schiffrin
Ernesto L
EL
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D014657:Vasculitis / Q000378:metabolism*
D019332:Endothelin-1