title: Impact of lysophosphatidylcholine on survival and function of UEA-1(+)acLDL (+) endothelial progenitor cells in patients with coronary artery disease.
abstract: 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 (40 μM). UEA-1(+)acLDL(+) EPCs were preincubated for 30 min with pravastatin (20 μM) with LY249002, a specific inhibitor of the Akt signaling pathway, and exposed for 24 h to LPC 40 μM. 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.
authors: Division of Cardiology, Kyung Hee University, Seoul, Republic of Korea.
authors: Seong Hun
authors: SH
authors: Hong
authors: Hyun Hee
authors: HH
authors: Jang
authors: So Ra
authors: SR
authors: Lee
authors: Kyung Hye
authors: KH
authors: Lee
authors: Jong Shin
authors: JS
authors: Woo
authors: Jin Bae
authors: JB
authors: Kim
authors: Woo-Shik
authors: WS
authors: Kim
authors: Byung Il
authors: BI
authors: Min
authors: Ki Ho
authors: KH
authors: Cho
authors: Kwon Sam
authors: KS
authors: Kim
authors: Xianwu
authors: X
authors: Cheng
authors: Weon
authors: W
authors: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000503:physiopathology*; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D037121:Plant Lectins / Q000378:metabolism*; D017035:Pravastatin / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D037121:Plant Lectins; C036850:Ulex europaeus lectins; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D017035:Pravastatin