ENDOTHELIAL SPECIFIC NOX2 OVER-EXPRESSION INCREASES SUSCEPTIBILITY TO ANGIOTENSIN II INDUCED AORTIC DISSECTION

2012 
Aortic dissection is a detrimental disease with high mortality. However, the mechanisms regulating the susceptibility to aortic dissection remain unknown. We hypothesise that endothelial oxidative stress due to the activation of the reactive oxygen species (ROS)-generating Nox2 enzyme play an important role in the development of aortic dissection. To investigate this, we generated transgenic mice (C57BL/6J background) with endothelial specific over-expression of Nox2 (Nox2-Tg) under the control of a tie-2 promoter. Expression of the human Nox2 transgene was confirmed by qRT-PCR to be found only in endothelial cells (EC) isolated from transgenic mice, and not in WT EC or vascular smooth muscle cells (VSMC) and macrophages isolated from either genotype. Wild-type (WT) littermates and Nox2-Tg male mice (6 months, n=11) were treated with vehicle or AngII (1 mg/kg/day) via subcutaneous mini-pump for 28 days. There was no significant difference in the pressor responses to AngII between WT and Nox2-Tg mice (WT 121±7 mm Hg vs Nox2-Tg 122±6 mm Hg). However, 5/11 Nox2-Tg mice developed aortic dissections compared to 0/11 WT mice after AngII infusion (p
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    0
    References
    0
    Citations
    NaN
    KQI
    []