Bony connection to vascular dysfunction and implications on hypertension

作     者：HUANG Yu (Institute of Vascular Medicine,Chinese University of Hong Kong,China) 

出 版 物：《岭南心血管病杂志》 (South China Journal of Cardiovascular Diseases)

年 卷 期：2011年第17卷第S1期

页      面：27-28页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：EDC COX EDR Bony connection to vascular dysfunction and implications on hypertension BMP over 

摘      要：Bone morphogenic protein 4（BMP4） belongs into the transforming growth factor-β（TGF-β） ***4 was originally discovered to par- ticipate in embryonic development,bone and cartilage ***4 is up-regulated in calcified atherosclerotic plaques and reduces endothelium-de-pendent ***4 can stimulate superoxide production and exert pro-inflammatory effects on the *** underlying mechanisms of how BMP4 mediates endothelial dysfunction and hypertension remain to be *** recent study shows that BMP treatment led to the impaired en-dothelium -dependent relaxations（EDR）,exaggerated endothelium-dependent contractions（EDC） and reactive oxygen species（ROS） generation in mouse aortas,which were reversed by BMP4 antagonist *** inhibition with thromboxane-prostanoid receptor antagonist or cyclooxygenase-2 （COX-2） but not cyclooxygenase-1（COX-1） inhibitor attenuates the BMP4-induced endothelial dysfunction which was further confirmed with the use of COX-1-/- or COX-2-/- *** and knockdown of BMP receptor 1A abolished EDC and COX-2 up-regulation in BMP4-treated mouse aortas. Apocynin and tempol treatment were effective in restoring EDR,preventing EDC,eliminating ROS over-production and COX-2 over-expression in BMP4-treated ***-2 inhibition blocked the effect of BMP4 without affecting BMP4-induced ROS over-production and COX-2 ***, renal arteries from hypertensive rats and humans showed higher levels of COX-2 and BMP4 accompanied by endothelial *** show for the first time that ROS serve as a pathological link between BMP4 stimulation and the downstream COX-2 up-regulation in endothelial cells,leading to endothelial *** BMP4/ROS/COX-2 cascade is important in the maintenance of endothelial dysfunction in hypertension.