In a previous study (Gitlin et al. Cardiovascular Res., 73:227, 2007), we reported the involvement of COX-2 in the formation of abdominal aortic aneurysms (AAAs). Furthermore, preliminary studies in our laboratory have indicated that B-arrestin2-mediated signaling leads to the induction of COX-2. In the present research, we have continued these studies and investigated the roles of B-arrestin2 and COX-2 in the formation of AAAs. AAA formation involves an abnormal dilation of the aorta, followed by macrophage infiltration and extensive remodeling of the vessel wall, which with time may lead to life-threatening AAA rupture. We have used a model of angiotensin II (AngII) induced AAAs in mice to study AAA formation and investigate the roles of B-arrestin2 and COX-2 in the induction of AAAs. We previously demonstrated that the deficiency of COX-2 attenuates the incidence AAAs in mice (Gitlin et al.), and furthermore that AngII induces significant COX-2 expression in the abdominal aortas of mice. Similar to our previous observation that COX-2-deficiency reduced AAA formation, our current studies show that the deficiency of B-arrestin2 significantly reduced AngII-induced AAA formation in mice. To identify possible mechanisms by which B-arrestin2 contributes to AAA formation, we have compared the induction of COX-2, ERK1/2 activation, NF-kB activation and STAT3 activation in B-arrestin2+/+ and -/- mice. Our conclusion to date is that the deficiency of B-arrestin2 may attenuate the incidence of AngII-induced AAAs by decreasing both B-arrestin2-mediated signaling, including the decreased induction of COX-2.
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