Original ArticleCritical Role of Prohibitin in Endothelial Cell Apoptosis Caused by Glycated Low-density Lipoproteins and Protective Effects of Grape Seed Procyanidin B2Yin, Wenbin PhD*; Li, Baoying PhD*; Li, Xiaoli PhD*; Yu, Fei PhD*; Cai, Qian PhD*; Zhang, Zhen PhD*; Wang, Junfu MS†; Zhang, Jianhua BS†; Zhou, Ruihai PhD‡; Cheng, Mei MD*; Gao, Haiqing MD*Author Information *Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China; †Institute of Basic Science, Medical Science Academy of Shandong, Jinan, China; and ‡Division of Cardiology, University of North Carolina at Chapel Hill, Chapel Hill, NC. Reprints: Haiqing Gao, MD, 107 Wenhuaxi Rd, Jinan 250012, Shandong Province, China (e-mail: firstname.lastname@example.org). Supported by National Natural Science Foundation of China (30873145, 81000340, 81100595), China Postdoctoral Science Foundation (20100471520, 2011M500748), and Natural Science Foundation of Shandong Province (Y2008C100, ZR2009CM036, ZR2010HQ067). The authors report no conflicts of interest. Received April 27, 2014 Accepted July 28, 2014 Journal of Cardiovascular Pharmacology: January 2015 - Volume 65 - Issue 1 - p 13-21 doi: 10.1097/FJC.0000000000000157 Buy Metrics Abstract Abstract: Elevated level of glycated low-density lipoproteins (glyLDL) is believed to contribute to endothelial dysfunction, which is involved in the pathogenesis and acceleration of diabetic vascular diseases. Grape seed procyanidin B2 (GSPB2) has been reported to possess protective effects against endothelial dysfunction. However, the underlying mechanism remains unclear. Prohibitin (PHB) is a multifunctional protein implicated in cellular survival and apoptosis. In this study, we showed that glyLDL treatment decreased protein level of PHB, reduced viability, and increased apoptosis in human umbilical vein endothelial cells (HUVEC). PHB overexpression or GSPB2 significantly attenuated apoptosis induced by glyLDL. Moreover, PHB siRNA increased HUVEC apoptosis, along with defective mitochondria and increased levels of cytosol cytochrome c concentration, caspase-3 activity, Bax/Bcl-2 ratio, and phosphorylated Akt, whereas PHB overexpression or GSPB2 restored these changes. Our study identified PHB as an important player responsible for HUVEC apoptosis induced by glyLDL. GSPB2 protected against HUVEC apoptosis at least in part through upregulating PHB. Targeting PHB could be significant in fighting against diabetic vascular complications. © 2015 by Lippincott Williams & Wilkins.