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Disturbed flow: p53 SUMOylation in the turnover of endothelial cells
Takabe, Wakako,Alberts-Grill, Noah,Jo, Hanjoong The Rockefeller University Press 2011 The Journal of cell biology Vol.193 No.5
<P>Disturbed blood flow induces apoptosis of vascular endothelial cells, which causes atherosclerosis. In this issue, Heo et al. (2011. <I>J. Cell Biol</I>. doi:10.1083/jcb.201010051) sheds light on p53’s role in this phenomenon. Disturbed flow induces peroxynitrite production, which activates protein kinase C ζ and it’s binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy). This leads to p53 SUMOylation and its export to the cytosol, where it binds to the antiapoptotic protein Bcl-2 to induce apoptosis.</P>
Anti-Inflammatory and Antiatherogenic Role of BMP Receptor II in Endothelial Cells
Kim, Chan Woo,Song, Hannah,Kumar, Sandeep,Nam, Douglas,Kwon, Hyuk Sang,Chang, Kyung Hwa,Son, Dong Ju,Kang, Dong-Won,Brodie, Seth A.,Weiss, Daiana,Vega, J. David,Alberts-Grill, Noah,Griendling, Kathy,T American Heart Association, Inc. 2013 Arteriosclerosis, thrombosis, and vascular biology Vol.33 No.6
<P><B>Objective—</B></P><P>Atherosclerosis is an inflammatory disease with multiple underlying metabolic and physical risk factors. Bone morphogenic protein 4 (BMP4) expression is increased in endothelium in atherosclerosis-prone regions and is known to induce endothelial inflammation, endothelial dysfunction, and hypertension. BMP actions are mediated by 2 different types of BMP receptors (BMPRI and BMPRII). Here, we show a surprising finding that loss of BMPRII expression causes endothelial inflammation and atherosclerosis.</P><P><B>Approach and Results—</B></P><P>Using BMPRII siRNA and BMPRII<SUP>+/−</SUP> mice, we found that specific knockdown of BMPRII, but not other BMP receptors (Alk1, Alk2, Alk3, Alk6, ActRIIa, and ActRIIb), induced endothelial inflammation in a ligand-independent manner by mechanisms mediated by reactive oxygen species, nuclear factor-KappaB, and reduced nicotinamide adenine dinucleotide phosphate oxidases. Further, BMPRII<SUP>+/−</SUP>ApoE<SUP>−/−</SUP> mice developed accelerated atherosclerosis compared with BMPRII<SUP>+/+</SUP>ApoE<SUP>−/−</SUP> mice. Interestingly, we found that multiple proatherogenic stimuli, such as hypercholesterolemia, disturbed flow, prohypertensive angiotensin II, and the proinflammatory cytokine (tumor necrosis factor-α), downregulated BMPRII expression in endothelium, whereas antiatherogenic stimuli, such as stable flow and statin treatment, upregulated its expression in vivo and in vitro. Moreover, BMPRII expression was significantly diminished in human coronary advanced atherosclerotic lesions. Also, we were able to rescue the endothelial inflammation induced by BMPRII knockdown by overexpressing the BMPRII wild type, but not by the BMPRII short form lacking the carboxyl-terminal tail region.</P><P><B>Conclusions—</B></P><P>These results suggest that BMPRII is a critical, anti-inflammatory, and antiatherogenic protein that is commonly targeted by multiple pro- and antiatherogenic factors. BMPRII may be used as a novel diagnostic and therapeutic target in atherosclerosis.</P>