Anti-Inflammatory and Antiatherogenic Role of BMP Receptor II in Endothelial Cells

• DOI: 10.1161/atvbaha.112.300287
• Publication Date: 2013-04-05T04:56:22Z
• Authors: Chan Woo Kim; Hannah Song; Sandeep Kumar; Douglas Nam; Hyuk Sang Kwon; Kyung Hwa Chang; Dong Ju Son; Dong-Won Kang; Seth A. Brodie; Daiana Weiss; J. David Vega; Noah Alberts-Grill; Kathy Griendling; W. Robert Taylor; Hanjoong Jo
• Keywords: Endothelial Dysfunction; Proinflammatory cytokine

Atherosclerosis is an inflammatory disease with multiple underlying metabolic and physical risk factors. Bone morphogenic protein 4 (BMP4) expression increased in endothelium atherosclerosis-prone regions known to induce endothelial inflammation, dysfunction, hypertension. BMP actions are mediated by 2 different types of receptors (BMPRI BMPRII). Here, we show a surprising finding that loss BMPRII causes inflammation atherosclerosis.Using siRNA BMPRII(+/-) mice, found specific knockdown BMPRII, but not other (Alk1, Alk2, Alk3, Alk6, ActRIIa, ActRIIb), induced ligand-independent manner mechanisms reactive oxygen species, nuclear factor-KappaB, reduced nicotinamide adenine dinucleotide phosphate oxidases. Further, BMPRII(+/-)ApoE(-/-) mice developed accelerated atherosclerosis compared BMPRII(+/+)ApoE(-/-) mice. Interestingly, proatherogenic stimuli, such as hypercholesterolemia, disturbed flow, prohypertensive angiotensin II, the proinflammatory cytokine (tumor necrosis factor-α), downregulated endothelium, whereas antiatherogenic stable flow statin treatment, upregulated its vivo vitro. Moreover, was significantly diminished human coronary advanced atherosclerotic lesions. Also, were able rescue overexpressing wild type, short form lacking carboxyl-terminal tail region.These results suggest critical, anti-inflammatory, commonly targeted pro- may be used novel diagnostic therapeutic target atherosclerosis.