Research Article

Concentration Polarization of Ox-LDL and Its Effect on Cell Proliferation and Apoptosis in Human Endothelial Cells

Shijie Liu, Jawahar L Mehta, Yubo Fan, Xiaoyan Deng and Zufeng Ding*

Published: 12/30/2016 | Volume 1 - Issue 1 | Pages: 011-018

ABSTRACT

Background: Flow-dependent concentration polarization of native LDL is important in the localization of atherogenesis. However, ox-LDL plays a more important role than n-LDL in atherogenesis by inducing cell proliferation and apoptosis. We hypothesized that concentration polarization of ox-LDL may adversely affect vascular beds due to its toxicity to endothelial cell (EC) lining.

Methods: Using a parallel-plate flow chamber technique, we studied water filtration rate and wall concentration of ox-LDLs EC monolayers cultured on permeable or non-permeable membranes. ECs cultured on permeable and non-permeable membranes were examined in terms of cell viability, ox-LDL uptake, LOX-1 expression and cell apoptosis (Cytochrome c and Bcl-2 expression). We observed that the wall concentration of ox-LDL was about 16% higher in the permeable group than in the permeable group (P<0.05). Cell proliferation (MTT assay) increased in response to low concentration of ox-LDL (1-5 μg/ml), and fell drastically in response to higher concentration; all these changes were more pronounced in the permeable group than in the non-permeable group. The uptake of ox-LDL and LOX-1 expression by ECs were also significantly higher in the permeable group than in the non-permeable group of cultured cells.

Conclusions: These observations suggest that concentration polarization of ox-LDL occurs in an artery that is permeable to water, and ox-LDL concentration polarization can enhance ox-LDL accumulation into the arterial wall and accelerate EC proliferation at low concentrations and apoptosis at high concentrations, possibly via LOX-1 expression.

Read Full Article HTML DOI: 10.29328/journal.jccm.1001003 Cite this Article

REFERENCES

  1. Chistiakov DA, Melnichenko A A, Orekhov AN, Bobryshev Y V. Paraoxonase and atherosclerosis-related cardiovascular diseases. Biochimie. 2017; 132: 19-27. Ref.: https://goo.gl/Y1CLFa
  2. Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders. Cardiovas Res. 2006; 69: 36-45. Ref.: https://goo.gl/uZOz8t
  3. Ding Z, Liu S, Wang X, Mathur P, Dai Y, et al. Cross-Talk between PCSK9 and Damaged mtDNA in Vascular Smooth Muscle Cells: Role in Apoptosis. Antioxid Redox Signal. 2016; 25 997-1008. Ref.: https://goo.gl/zjwncZ
  4. Ding Z, Liu S, Wang X, Deng X, Fan Y, et al. Cross-talk between LOX-1 and PCSK9 in vascular tissues. Cardiovasc Res. 2015; 107: 556-567. Ref.: https://goo.gl/jzNZVd  
  5. Chistiakov DA, Orekhov AN, Bobryshev YV. LOX-1-Mediated Effects on Vascular Cells in Atherosclerosis. Cell Physiol Biochem. 2016; 38: 1851-1859. Ref.: https://goo.gl/hukwv1
  6. Cobbold CA, Sherratt JA, Maxwell SR. Lipoprotein oxidation and its significance for atherosclerosis: a mathematical approach. Bull Math Biol. 2002; 64: 65-95. Ref.: https://goo.gl/PTDi3B  
  7. Chen XP, Xun KL, Wu Q, Zhang TT, Shi JS, et al. Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: Role of reactive oxygen species. Vasc Pharmacol. 2007; 47: 1-9. Ref.: https://goo.gl/o77VPB
  8. Dimmeler S, Zeiher AM. Endothelial cell apoptosis in angiogenesis and vessel regression. Circ Res. 2000; 87: 434-439. Ref.: https://goo.gl/6OsOkr
  9. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362: 801-809. Ref.: https://goo.gl/MDN1Xk
  10. Essler M, Retzer M, Bauer M, Heemskerk JW, Aepfelbacher M, et al. Mildly oxidized low density lipoprotein induces contraction of human endothelial cells through activation of Rho/Rho kinase and inhibition of myosin light chain phosphatase. J Biol Chem. 1999; 274: 30361-30364. Ref.: https://goo.gl/rC2x0v
  11. Zhao B, Ehringer WD, Dierichs R, Miller FN. Oxidized low-density lipoprotein increases endothelial intracellular calcium and alters cytoskeletal F-actin distribution. Eur J Clin Invest. 1997; 27: 48-54. Ref.: https://goo.gl/4Q0JSw
  12. Galle J, Heinloth A, Wanner C, Heermeier K. Dual effect of oxidized LDL on cell cycle in human endothelial cells through oxidative stress. Kidney Int Suppl. 2001; 78: 120-123. Ref.: https://goo.gl/zic9cI
  13. Dzau VJ, Braun-Dullaeus RC, Sedding DG. Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies. Nat Med. 2002; 8: 1249-1256. Ref.: https://goo.gl/Oe4mzG
  14. Ding Z, Liu S, Deng X, Fan Y, Wang X, et al. Hemodynamic shear stress modulates endothelial cell autophagy: Role of LOX-1. Int J Cardiol. 2015; 1: 86-95. Ref.: https://goo.gl/PJUIaF
  15. Kleinstreuer C, Hyun S, Buchanan JR Jr, Longest PW, Archie JP Jr, et al. Hemodynamic parameters and early intimal thickening in branching blood vessels. Crit Rev Biomed Eng. 2001; 29: 1-64. Ref.: https://goo.gl/tT26O5
  16. Ku DN, Giddens DP. Pulsatile flow in a model carotid bifurcation. Arteriosclerosis. 1983; 3: 31-39. Ref.: https://goo.gl/HGPmp7
  17. Hyun S, Kleinstreuer C, Archie JP Jr. Computational particle-hemodynamics analysis and geometric reconstruction after carotid endarterectomy. Comput Biol Med. 2001; 31: 365-384. Ref.: https://goo.gl/1tePMz
  18. Deng X, Marois Y, How T, Merhi Y, King M, et al. Luminal surface concentration of lipoprotein (LDL) and its effect on the wall uptake of cholesterol by canine carotid arteries. J Vasc Surg. 1995; 21: 135-145. Ref.: https://goo.gl/a00uVh
  19. Ding Z, Liu S, Wang X, Deng X, Fan Y, et al. Hemodynamic shear stress via ROS modulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta. Antioxid Redox Signal. 2015; 22: 760-771. Ref.: https://goo.gl/bbI3e3
  20. Hafiane A, Genest J. High density lipoproteins: Measurement techniques and potential biomarkers of cardiovascular risk. BBA Clin. 2015; 31: 175-188. Ref.: https://goo.gl/eX587z
  21. Cominacini L, Garbin U, Davoli A, Micciolo R, Bosello O, et al. A simple test for predisposition to LDL oxidation based on the fluorescence development during copper-catalyzed oxidative modification. J Lipid Res. 1991; 32: 349-358. Ref.: https://goo.gl/VawjTD
  22. Ding Z, Liu S, Wang X, Dai Y, Khaidakov M, et al. LOX-1, mtDNA damage, and NLRP3 inflammasome activation in macrophages: implications in atherogenesis. Cardiovasc Res. 2014; 103: 619-628. Ref.: https://goo.gl/AudeOr
  23. Xavier HT, Abdalla DS, Martinez TL, Ramires JA, Gagliardi AR. Effects of oxidized LDL on in vitro proliferation and spontaneous motility of human coronary artery endothelial cells. Arq Bras Cardiol. 2004; 83: 493-497. Ref.: https://goo.gl/jbzG1a  
  24. Dandapat A, Hu C, Sun L, Mehta JL. Small concentrations of oxLDL induce capillary tube formation from endothelial cells via LOX-1-dependent redox-sensitive pathway. Arterioscler Thromb Vasc Biol. 2007; 27: 2435-2442. Ref.: https://goo.gl/bRtQ65
  25. Hoff HF, O'Neil JA. Oxidation of LDL: role in atherogenesis. Klin Wochenschf. 1991; 69: 1032-1038. Ref.: https://goo.gl/QbT220
  26. Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, et al. An endothelial receptor for oxidized low-density lipoprotein. Nature. 1997; 386: 73-77. Ref.: https://goo.gl/WY4hsp
  27. Ding Z, Liu S, Wang X, Khaidakov M, Dai Y, et al. Oxidant stress in mitochondrial DNA damage, autophagy and inflammation in atherosclerosis. Sci Rep. 2013; 3: 1077. Ref.: https://goo.gl/mzir86
  28. Moriwaki H, Kume N, Sawamura T, Aoyama T, Hoshikawa H, et al. Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein. Arterioscler Thromb Vasc Biol. 1998; 18: 1541-1547. Ref.: https://goo.gl/37cwpW