Mechanobiology of Endothelial Cells Related to the Formation of Arterial Disease

  • Noriyuki KataokaEmail author


Atherosclerosis is a serious disease that causes cardiovascular diseases such as cerebral infarction and myocardial infarction. Endothelial cell injury is the first step in atherogenesis by inducing increase in the production of chemoattractant proteins and adhesion molecules to leukocytes (Ross, Nature 362 (6423): 801–809, 1993). One of the key events in atherogenesis is the recruitment of blood leukocytes, especially monocytes, to proatherogenic vascular regions (Swirski et al, J Clin Invest 117:195–205, 2007; Tacke et al, J Clin Invest 117:185–194, 2007) and their subsequent transmigration across endothelial cells. Interactions between leukocytes and endothelial cells involve multi-step processes including rolling, adhesion, locomotion, and transmigration. Therefore, mechanics and dynamics of endothelial cells and monocytes are important matters to understand the whole process of atherogenesis. Here, we show and discuss the mechanobiology of endothelial cells related to the formation of arterial disease.


Atherogenesis Endothelial cell Monocyte Mechanobiology 


  1. Bradfield PF, Scheiermann C, Nourshargh S, Ody C, Luscinskas FW, Rainger GE, Nash GB, Miljkovic-Licina M, Aurrand-Lions M, Imhof BA (2007) JAM-C regulates unidirectional monocyte transendothelial migration in inflammation. Blood 110:2545–2555CrossRefPubMedPubMedCentralGoogle Scholar
  2. Giaever I, Keese CR (1991) Micromotion of mammalian cells measured electrically. Proc Natl Acad Sci U S A 88:7896–7900CrossRefPubMedPubMedCentralGoogle Scholar
  3. Hashimoto K, Kataoka N, Nakamura E, Asahara H, Ogasawara Y, Tsujioka K, Kajiya F (2004) Direct observation and quantitative analysis of spatiotemporal dynamics of individual living monocytes during transendothelial migration. Atherosclerosis 177:19–27CrossRefPubMedGoogle Scholar
  4. Hashimoto K, Kataoka N, Nakamura E, Tsujioka K, Kajiya F (2007) Oxidized LDL specifically promotes the initiation of monocyte invasion during transendothelial migration with upregulated PECAM-1 and downregulated VE-cadherin on endothelial junctions. Atherosclerosis 194:e9–e17CrossRefPubMedGoogle Scholar
  5. Hashimoto K, Kataoka N, Nakamura E, Hagihara K, Okamoto T, Kanouchi H, Mohri S, Tsujioka K, Kajiya F (2012) Live-cell visualization of the trans-cellular mode of monocyte transmigration across the vascular endothelium, and its relationship with endothelial PECAM-1. J Physiol Sci 62(1):63–69CrossRefPubMedGoogle Scholar
  6. Huang MT, Larbi KY, Scheiermann C, Woodfin A, Gerwin N, Haskard DO, Nourshargh S (2006) ICAM-2 mediates neutrophil transmigration in vivo: evidence for stimulus specificity and a role in PECAM-1-independent transmigration. Blood 107:4721–4727CrossRefPubMedGoogle Scholar
  7. Kataoka N, Iwaki K, Hashimoto K, Mochizuki S, Ogasawara Y, Sato M, Tsujioka K, Kajiya F (2002) Measurements of endothelial cell-to-cell and cell-to-substrate gaps and micromechanical properties of endothelial cells during monocyte adhesion. Proc Natl Acad Sci U S A 99:15638–15643CrossRefPubMedPubMedCentralGoogle Scholar
  8. Keiper T, Al-Fakhri N, Chavakis E, Athanasopoulos AN, Isermann B, Herzog S, Saffrich R, Hersemeyer K, Bohle RM, Haendeler J, Preissner KT, Santoso S, Chavakis T (2005) The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment. FASEB J 19:2078–2080PubMedGoogle Scholar
  9. Klouche M, May AE, Hemmes M, Messner M, Kanse SM, Preissner KT, Bhakdi S (1999) Enzymatically modified, nonoxidized LDL induces selective adhesion and transmigration of monocytes and T-lymphocytes through human endothelial cell monolayers. Arterioscler Thromb Vasc Biol 19:784–793CrossRefPubMedGoogle Scholar
  10. Mamdouh Z, Chen X, Pierini LM, Maxfield FR, Muller WA (2003) Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis. Nature 421:748–753CrossRefPubMedGoogle Scholar
  11. Mamdouh Z, Kreitzer GE, Muller WA (2008) Leukocyte transmigration requires kinesin-mediated microtubule-dependent membrane trafficking from the lateral border recycling compartment. J Exp Med 205:951–966CrossRefPubMedPubMedCentralGoogle Scholar
  12. Muller WA, Weigl SA, Deng X, Phillips DM (1993) PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med 178:449–460CrossRefPubMedGoogle Scholar
  13. Radmacher M, Fritz M, Kacher CM, Cleveland JP, Hansma PK (1996) Measuring the viscoelastic properties of human platelets with the atomic force microscope. Biophys J 70:556–567CrossRefPubMedPubMedCentralGoogle Scholar
  14. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809CrossRefPubMedGoogle Scholar
  15. Schenkel AR, Mamdouh Z, Chen X, Liebman RM, Muller WA (2002) CD99 plays a major role in the migration of monocytes through endothelial junctions. Nat Immunol 3:143–150CrossRefPubMedGoogle Scholar
  16. Shaw SK, Bamba PS, Perkins BN, Luscinskas FW (2001) Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium. J Immunol 167:2323–2330CrossRefPubMedGoogle Scholar
  17. Su WH, Chen HI, Jen CJ (2002) Differential movements of VE-cadherin and PECAM-1 during transmigration of polymorphonuclear leukocytes through human umbilical vein endothelium. Blood 100:3597–3603CrossRefPubMedGoogle Scholar
  18. Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ (2007) Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 117:195–205CrossRefPubMedPubMedCentralGoogle Scholar
  19. Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodra J, Garin A, Liu J, Mack M, van Rooijen N, Lira SA, Habenicht AJ, Randolph GJ (2007) Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 117:185–194CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Japan 2016

Authors and Affiliations

  1. 1.Department of Mechanical Engineering, College of EngineeringNihon UniversityKoriyamaPrefecture Japan

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