caa a22 4500 606220488 CHVBK 20210128101124.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00380-014-0473-z doi (NATIONALLICENCE)springer-10.1007/s00380-014-0473-z Impact of lysophosphatidylcholine on survival and function of UEA-1+acLDL+ endothelial progenitor cells in patients with coronary artery disease [Elektronische Daten] [Seong Hong, Hyun Jang, So Lee, Kyung Lee, Jong Woo, Jin Kim, Woo-Shik Kim, Byung Min, Ki Cho, Kwon Kim, Xianwu Cheng, Weon Kim] Lysophosphatidylcholine (LPC) generated from oxidized low-density lipoprotein by lipoprotein-associated phospholipase A2 plays a key role in plaque inflammation and vulnerability. Endothelial progenitor cells (EPCs) can repair injured endothelium and exert anti-inflammatory effects of vulnerable plaque. We study the impact and mechanisms of LPC on UEA-1 and acLDL binding EPCs (UEA-1+acLDL+ EPCs). UEA-1+acLDL+ EPCs from coronary artery disease (CAD) patients were cultured and exposed to LPC at different concentrations and different timepoints. We determined the significant concentration (40μM). UEA-1+acLDL+ EPCs were preincubated for 30min with pravastatin (20μM) with LY249002, a specific inhibitor of the Akt signaling pathway, and exposed for 24h to LPC 40μM. The survival, migration, adhesion, and proliferation of UEA-1+acLDL+ EPCs were assessed. To examine the mechanisms of LPC toxicity and pravastatin effects, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels and the ratio of Bcl-2/Bax protein expression were assessed. LPC induced apoptosis and impaired migration and adhesion of UEA-1+acLDL+ EPCs significantly. The detrimental effects of LPC were attenuated by pravastatin. However, when UEA-1+acLDL+ EPCs were pretreated with pravastatin and LY249002, a specific inhibitor of the Akt signaling pathway, simultaneously, the beneficial effects of pravastatin were abolished. Furthermore, LPC suppressed Akt and eNOS phosphorylation and increased Bcl-2/Bax expression. The effects of LPC on Akt/eNOS and Bcl-2/Bax activity were reversed by pravastatin. In conclusion, LPC inhibited UEA-1+acLDL+ EPCs survival and impaired its functions, and these were attributable to inhibition of the Akt/eNOS and Bcl-2/Bax pathway. Pravastatin reversed the detrimental action of LPC. These findings suggest that LPC inhibition can be a possible strategy for CAD through EPC revitalization. Springer Japan, 2014 Lysophosphatidylcholine nationallicence Endothelial progenitor cell nationallicence Pravastatin nationallicence Coronary artery disease nationallicence Vulnerable plaque nationallicence Hong Seong Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Jang Hyun Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Lee So Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Lee Kyung Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Woo Jong Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Kim Jin Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Kim Woo-Shik Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Min Byung Cardiovascular Division, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, #1 Hoegi-Dong, Dongdaemoon-Gu, 130-702, Seoul, Republic of Korea aut Cho Ki Department of Cardiovascular and Neurologic Disease, Hospital of Korean Medicine, Seoul, Republic of Korea aut Kim Kwon Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Cheng Xianwu Nagoya University Graduate School of Medicine, Nagoya, Japan aut Kim Weon Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut Heart and Vessels Springer Japan 30/1(2015-01-01), 115-125 0910-8327 30:1<115 2015 30 380 https://doi.org/10.1007/s00380-014-0473-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00380-014-0473-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hong Seong Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Jang Hyun Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lee So Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lee Kyung Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Woo Jong Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Jin Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Woo-Shik Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Min Byung Cardiovascular Division, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, #1 Hoegi-Dong, Dongdaemoon-Gu, 130-702, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Cho Ki Department of Cardiovascular and Neurologic Disease, Hospital of Korean Medicine, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Kwon Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Cheng Xianwu Nagoya University Graduate School of Medicine, Nagoya, Japan aut NATIONALLICENCE 700 1- Kim Weon Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea aut NATIONALLICENCE 773 0- Heart and Vessels Springer Japan 30/1(2015-01-01), 115-125 0910-8327 30:1<115 2015 30 380