Skip to main content

Vascular shear stress and activation of inflammatory genes

Abstract

Atherosclerotic lesions form preferentially at distinct sites in the arterial tree, especially at or near branch points, bifurcations, and curvatures where there is disturbed or oscillatory blood flow. In contrast, straight regions of the vasculature exhibit uniform laminar shear stress, which is atheroprotective. The ability of laminar flow to exert an anti-inflammatory effect on the endothelial cell lining of the blood vessel is revealed by preventing monocyte adhesion, proliferation, and apoptosis. Changes in endothelial cell gene expression in response to laminar shear stress reflect these changes in cell physiology with the demonstration that physiologic flow inhibits the expression of inflammatory genes. Thus, shear stress is critically important in regulating vascular physiology and pathobiology of the vessel wall via the modulation of endothelial cell gene expression.

This is a preview of subscription content, access via your institution.

References and Recommended Reading

  1. Ross R: Atherosclerosis—an inflammatory disease. N Engl J Med 1999, 340:115–126.

    PubMed  Article  CAS  Google Scholar 

  2. Ross R: The pathogensis of atherosclerosis: a perspective for the 1990s. Nature 1993, 362:801–809.

    PubMed  Article  CAS  Google Scholar 

  3. Cornhil JF, Roach MR: A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta. Atherosclerosis 1976, 23:489–501.

    Article  Google Scholar 

  4. Glagov S, Zarins C, Giddens DP, et al.: Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 1988, 112:1018–1031.

    PubMed  CAS  Google Scholar 

  5. Hajra L, Evans AI, Chen M, et al.: The NF-kB signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci U S A 2000, 97:9052–9057.

    PubMed  Article  CAS  Google Scholar 

  6. Iiyama K, Hajra L, Liyama M, et al.: Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 1999, 85:199–207.

    PubMed  CAS  Google Scholar 

  7. Nagel T, Resnick N, Dewey CF, et al.: Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arteriosler Thromb Vasc Biol 1999, 19:1825–1834.

    CAS  Google Scholar 

  8. Chen XL, Varner SE, Rao AS, et al.: Laminar flow induction of antioxidant response element-mediated genes in endothelial cells. A novel anti-inflammatory mechanism. J Biol Chem 2003, 278:703–711.

    PubMed  Article  CAS  Google Scholar 

  9. Liu Y, Zhu Y, Rannou F, et al.: Laminar flow activates peroxisome proliferator-activated receptor-gamma in vascular endothelial cells. Circulation 2003, 110:1128–1133.

    Article  CAS  Google Scholar 

  10. Akaike M, Che W, Marmarosh NL, et al.: The hinge-helix 1 region of peroxisome proliferator-activated receptor gamma1 (PPARgamma1) mediates interaction with extracellular signal-regulated kinase 5 and PPARgamma1 transcriptional activation: involvement in flow-induced PPARgamma activation in endothelial cells. Mol Cell Biol 2004, 24:8691–8704.

    PubMed  Article  CAS  Google Scholar 

  11. Ranjan V, Diamond SL: Fluid shear stress induces synthesis and nuclear localization of c-fos in cultured human endothelial cells. Biochem Biophys Res Comm 1993, 196:79–84.

    PubMed  Article  CAS  Google Scholar 

  12. Liu Y, Chen BP, Lu M, et al.: Shear stress activation of SREBP1 in endothelial cells is mediated by integrins. Arterioscler Thromb Vasc Biol 2002, 22:76–81.

    PubMed  Article  Google Scholar 

  13. Lan Q, Mercurius KO, Davies PF: Stimulation of transcription factors NF kappa B and AP1 in endothelial cells subjected to shear stress. Biochem Biophys Res Comm 1994, 201:950–956.

    PubMed  Article  CAS  Google Scholar 

  14. Hsieh HJ, Li NQ, Frangos JA: Shear-induced platelet-derived growth factor gene expression in human endothelial cells is mediated by protein kinase C. J Cell Physiol 1992, 150:152–158.

    Article  Google Scholar 

  15. Poston RN, Haskar DO, Coucher JR, et al.: Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Path 1992, 140:665–673.

    PubMed  CAS  Google Scholar 

  16. O’Brien KD, McDonald TO, Chait A, et al.: Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation 1996, 93:672–682.

    PubMed  CAS  Google Scholar 

  17. Brooks AR, Lelkes PI, Rubanyi GM: Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol Genomics 2002, 9:22–41.

    Google Scholar 

  18. Sampath R, Kukielka GL, Smith CW, et al.: Shear stress-mediated changes in the expression of leukocyte adhesion receptors on human umbilical vein endothelial cells in vitro. Ann Biomed Eng 1995, 23:247–256.

    PubMed  Article  CAS  Google Scholar 

  19. Sorescu GP, Sykes M, Weiss D, et al.: Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response. J Biol Chem 2003, 278:31128–31135.

    PubMed  Article  CAS  Google Scholar 

  20. Walpola PL, Gotlieb AI, Cybulsky MI, et al.: Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress. Arterioscler Thromb Vasc Biol 1995, 15:2–10.

    PubMed  CAS  Google Scholar 

  21. Elrayess MA, Webb KE, Flavell DM, et al.: A novel functional polymorphism in the PECAM-1 gene (53G>A) is associated with progression of atherosclerosis in the LOCAT and REGRESS studies. Atherosclerosis 2003, 168:131–138.

    PubMed  Article  CAS  Google Scholar 

  22. Tzima E, Irani-Tehrani M, Kiosses WB, et al.: A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 2005, 437:426–431.

    PubMed  Article  CAS  Google Scholar 

  23. Yamawaki H, Lehoux S, Berk BC: Chronic physiological shear stress inhibits tumor necrosis factor-induced proinflammatory responses in rabbit aorta perfused ex vivo. Circulation 2003, 108:1619–1625.

    PubMed  Article  CAS  Google Scholar 

  24. Surapisitchat J, Hoefen RJ, Pi X, et al.: Fluid shear stress inhibits TNF-alpha activation of JNK but not ERK1/2 or p38 in human umbilical vein endothelial cells: Inhibitory crosstalk among MAPK family members. Proc Natl Acad Sci USA 2001, 98:6476–6481.

    PubMed  Article  CAS  Google Scholar 

  25. Gosling J, Slaymaker S, Gu L, et al.: MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 1999, 103:773–778.

    PubMed  CAS  Article  Google Scholar 

  26. Chen XL, Grey JY, Thomas S, et al.: Sphingosine kinase-1 mediates TNF-alpha-induced MCP-1 gene expression in endothelial cells: upregulation by oscillatory flow. Am J Physiol Heart Circ Physiol 2004, 287:H1452-H1458.

    PubMed  Article  CAS  Google Scholar 

  27. Sorescu GP, Song H, Tressel SL, et al.: Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase. Circ Res 2004, 95:773–779.

    PubMed  Article  CAS  Google Scholar 

  28. Melchionna R, Porcelli D, Mangoni A, et al.: Laminar shear stress inhibits CXCR4 expression on endothelial cells: functional consequences for atherogenesis. FASEB J 2005, 19:629–631.

    PubMed  CAS  Google Scholar 

  29. Akimoto S, Mitsumata M, Sasaguri T, et al.: Laminar shear stress inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21(Sdi1/Cip1/Waf1). Circ Res 2000, 86:185–190.

    PubMed  CAS  Google Scholar 

  30. Davies PF, Remuzzi A, Gordon EJ, et al.: Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc Natl Acad Sci USA 1986, 83:2114–2117.

    PubMed  Article  CAS  Google Scholar 

  31. Wasserman SM, Mehraban F, Komuves LG, et al.: Gene expression profile of human endothelial cells exposed to sustained fluid shear stress. Physiol Genomics 2002, 12:13–23.

    PubMed  CAS  Google Scholar 

  32. Andersson M, Karlsson L, Svensson PA, et al.: Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure. J Vasc Res 2005, 42:441–452.

    PubMed  Article  CAS  Google Scholar 

  33. Chen BP, Li YS, Zhao Y, et al.: DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Physiol Genomics 2001, 7:55–63.

    PubMed  Article  CAS  Google Scholar 

  34. Bombeli T, Schwartz BR, Harlan JM: Endothelial cells undergoing apoptosis become proadhesive for nonactivated platelets. Blood 1999, 93:3831–3838.

    PubMed  CAS  Google Scholar 

  35. Dardik A, Chen L, Frattini J, et al.: Differential effects of orbital and laminar shear stress on endothelial cells. J Vasc Surg 2005, 41:869–880.

    PubMed  Article  Google Scholar 

  36. Jin X, Mitsumata M, Yamane T, et al.: Induction of human inhibitor of apoptosis protein-2 by shear stress in endothelial cells. FEBS Lett 2002, 529:286–292.

    PubMed  Article  CAS  Google Scholar 

  37. Beere HM, Green DR: Stress management—heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol 2001, 11:6–10.

    PubMed  Article  CAS  Google Scholar 

  38. Urbich C, Walter DH, Zeiher AM, et al.: Laminar shear stress upregulates integrin expression: role in endothelial cell adhesion and apoptosis. Circ Res 2000, 87:683–689.

    PubMed  CAS  Google Scholar 

  39. García-Cardeña G, Comander J, Anderson KR, et al.: Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proc Natl Acad Sci U S A 2001, 98:4478–4485.

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Bradford C. Berk MD, PhD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

World, C.J., Garin, G. & Berk, B.C. Vascular shear stress and activation of inflammatory genes. Curr Atheroscler Rep 8, 240–244 (2006). https://doi.org/10.1007/s11883-006-0079-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-006-0079-8

Keywords

  • Shear Stress
  • Atherosclerotic Lesion
  • Arterioscler Thromb Vasc Biol
  • Fluid Shear Stress
  • Monocyte Adhesion