PT  - JOURNAL ARTICLE
AU  - Lars Bellner
AU  - Lucia Martinelli
AU  - Adna Halilovic
AU  - Kiran Patil
AU  - Nitin Puri
AU  - Michael W. Dunn
AU  - Raymond F. Regan
AU  - Michal Laniado Schwartzman
TI  - Heme Oxygenase-2 Deletion Causes Endothelial Cell Activation Marked by Oxidative Stress, Inflammation, and Angiogenesis
AID  - 10.1124/jpet.109.158352
DP  - 2009 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 925--932
VI  - 331
IP  - 3
4099  - http://jpet.aspetjournals.org/content/331/3/925.short
4100  - http://jpet.aspetjournals.org/content/331/3/925.full
SO  - J Pharmacol Exp Ther2009 Dec 01; 331
AB  - In previous studies, we have shown that heme oxygenase (HO)-2 null [HO-2(−/−)] mice exhibit a faulty response to injury; chronic inflammation and massive neovascularization replaced resolution of inflammation and tissue repair. Endothelial cells play an active and essential role in the control of inflammation and the process of angiogenesis. We examined whether HO-2 deletion affects endothelial cell function. Under basal conditions, HO-2(−/−) aortic endothelial cells (mAEC) showed a 3-fold higher expression of vascular endothelial growth factor receptor 1 and a marked angiogenic response compared with wild-type (WT) cells. Compared with WT cells, HO-2(−/−) mAEC showed a 2-fold reduction in HO activity and marked increases in levels of gp91phox/NADPH oxidase isoform, superoxide, nuclear factor κB activation, and expression of inflammatory cytokines, including interleukin (IL)-1α and IL-6. HO-2 deletion transforms endothelial cells from a “normal” to an “activated” phenotype characterized by increases in inflammatory, oxidative, and angiogenic factors. This switch may be the result of reduced HO activity and the associated reduction in the cytoprotective HO products, carbon monoxide and biliverdin/bilirubin, because addition of biliverdin to HO-2(−/−) cells attenuated angiogenesis and reduced superoxide production. This transformation underscores the importance of HO-2 in the regulation of endothelial cell homeostasis.© 2009 by The American Society for Pharmacology and Experimental Therapeutics