Impact of lysophosphatidylcholine on survival and function of UEA-1+acLDL+ endothelial progenitor cells in patients with coronary artery disease

详细信息    查看全文

• 作者：Seong Hun Hong ; Hyun Hee Jang ; So Ra Lee ; Kyung Hye Lee ; Jong Shin Woo…
• 关键词：Lysophosphatidylcholine ; Endothelial progenitor cell ; Pravastatin ; Coronary artery disease ; Vulnerable plaque
• 刊名：Heart and Vessels
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：30
• 期：1
• 页码：115-125
• 全文大小：1,450 KB
• 参考文献：1. Rabbani R, Topol EJ (1999) Strategies to achieve coronary arterial plaque stabilization. Cardiovasc Res 41:402-17 CrossRef
  2. Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R (2010) Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30:1282-292 CrossRef
  3. Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Menzoian JO, Vita JA (2002) Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation 105:1567-572 CrossRef
  4. Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD (1990) Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature 344:160-62 CrossRef
  5. Hsieh CC, Yen MH, Liu HW, Lau YT (2000) Lysophosphatidylcholine induces apoptotic and non-apoptotic death in vascular smooth muscle cells: in comparison with oxidized LDL. Atherosclerosis 151:481-91 CrossRef
  6. Gon?alves I, Edsfeldt A, Ko NY, Grufman H, Berg K, Bj?rkbacka H, Nitulescu M, Persson A, Nilsson M, Prehn C, Adamski J, Nilsson J (2012) Evidence supporting a key role of Lp-PLA2-generated lysophosphatidylcholine in human atherosclerotic plaque inflammation. Arterioscler Thromb Vasc Biol 32:1505-512 CrossRef
  7. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964-67 CrossRef
  8. Vasa M, Fichtlscherer S, Aicher A, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–E7 CrossRef
  9. Briguori C, Testa U, Riccioni R, Colombo A, Petrucci E, Condorelli G, Mariani G, D’Andrea D, De Micco F, Rivera NV, Puca AA, Peschle C, Condorelli G (2010) Correlations between progression of coronary artery disease and circulating endothelial progenitor cells. FASEB J 24(6):1981-988 CrossRef
  10. Chen MC, Chen CJ, Yang CH, Liu WH, Fang CY, Hsieh YK, Chang HW (2008) Relationship of the percentage of circulating endothelial progenitor cell to the severity of coronary artery disease. Heart Vessels 23(1):47-2 CrossRef
  11. Ma ZL, Mai XL, Sun JH, Ju SH, Yang X, Ni Y, Teng GJ (2009) Inhibited atherosclerotic plaque formation by local administration of magnetically labeled endothelial progenitor cells (EPCs) in a rabbit model. Atherosclerosis 205(1):80-6 CrossRef
  12. Fadini GP, Agostini C, Sartore S, Avogaro A (2007) Endothelial progenitor cells in the natural history of atherosclerosis. Atherosclerosis 194(1):46-4 CrossRef
  13. Wang X, Chen J, Tao Q, Zhu J, Shang Y (2004) Effects of ox-LDL on number and activity of circulating endothelial progenitor cells. Drug Chem Toxicol 27(3):243-55 CrossRef
  14. Tie G, Yan J, Yang Y, Park BD, Messina JA, Raffai RL, Nowicki PT, Messina LM (2010) Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res 47(6):519-30 CrossRef
  15. Ma FX, Zhou B, Chen Z, Ren Q, Lu SH, Sawamura T, Han ZC (2006) Oxidized low density lipoprotein im
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Cardiology
  Cardiac Surgery
  Vascular Surgery
  Biomedical Engineering
  Interventional Radiology
  Ultrasound
  
• 出版者：Springer Japan
• ISSN：1615-2573

文摘

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.