|
|
Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2002-01-0046.
 Previous Article | Table of Contents | Next Article 
Blood, 1 September 2002, Vol. 100, No. 5, pp. 1689-1698
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Prolonged fluid shear stress induces a distinct set of
endothelial cell genes, most specifically lung Krüppel-like
factor (KLF2)
Rob J. Dekker,
Simone van Soest,
Ruud D. Fontijn,
Sonia Salamanca,
Philip G. de
Groot,
Ed VanBavel,
Hans Pannekoek, and
Anton J. G. Horrevoets
From the Departments of Biochemistry and Medical
Physics, Academic Medical Center, University of Amsterdam, The
Netherlands; and the Department of Hematology, University Medical
Center, Utrecht, The Netherlands.
The endothelium expresses a large repertoire of genes under
apparent transcriptional control of biomechanical forces, many of which
are neither cell-type nor flow specific. We set out to identify genes
that are uniquely flow responsive in human vascular endothelial cells.
Transcriptional profiling using commercial DNA microarrays identified
12 of 18 000 genes that were modulated at least 5-fold after 24 hours
of steady laminar flow (25 dyne/cm2). After a 7-day
exposure to unidirectional pulsatile flow (19 ± 12 dyne/cm2), only 3 of 12 remained elevated at least 5-fold.
A custom microarray of ~300 vascular cell-related gene fragments was
constructed, and expression analysis revealed that many flow-induced
genes are also induced by at least one of the following agents: tumor necrosis factor- (TNF-), interleukin-1 (IL-1),
transforming growth factor-, vascular endothelial growth factor, or
thrombin, indicating a more general role in adaptive or stress
responses. Most flow-induced genes were also induced by TNF- but not
IL-1, suggesting the involvement of reactive oxygen species. A
limited panel of genes that are unique for flow-exposed cultures was
identified, including lung Krüppel-like factor
(LKLF/KLF2) and cytochrome P450 1B1 (CYP1B1).
In marked contrast, both these genes were substantially repressed
by TNF-. LKLF but not CYP1B1 mRNA was detected
exclusively in the vascular endothelium of healthy human aorta by in
situ hybridization and appeared to be flow regulated. To date LKLF is
the first endothelial transcription factor that is uniquely induced by
flow and might therefore be at the molecular basis of the physiological
healthy, flow-exposed state of the endothelial cell.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A.-M. Teichert, J. A. Scott, G. B. Robb, Y.-Q. Zhou, S.-N. Zhu, M. Lem, A. Keightley, B. M. Steer, A. C. Schuh, S. L. Adamson, et al.
Endothelial Nitric Oxide Synthase Gene Expression During Murine Embryogenesis: Commencement of Expression in the Embryo Occurs With the Establishment of a Unidirectional Circulatory System
Circ. Res.,
July 3, 2008;
103(1):
24 - 33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. O. Fledderus, R. A. Boon, O. L. Volger, H. Hurttila, S. Yla-Herttuala, H. Pannekoek, A.-L. Levonen, and A. J.G. Horrevoets
KLF2 Primes the Antioxidant Transcription Factor Nrf2 for Activation in Endothelial Cells
Arterioscler. Thromb. Vasc. Biol.,
July 1, 2008;
28(7):
1339 - 1346.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. D. Wagner and P. S. Frenette
The vessel wall and its interactions
Blood,
June 1, 2008;
111(11):
5271 - 5281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Kinderlerer, F. Ali, M. Johns, E. A. Lidington, V. Leung, J. J. Boyle, S. S. Hamdulay, P. C. Evans, D. O. Haskard, and J. C. Mason
KLF2-dependent, Shear Stress-induced Expression of CD59: A NOVEL CYTOPROTECTIVE MECHANISM AGAINST COMPLEMENT-MEDIATED INJURY IN THE VASCULATURE
J. Biol. Chem.,
May 23, 2008;
283(21):
14636 - 14644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Liu, M. S. Kluger, A. D'Alessio, G. Garcia-Cardena, and J. S. Pober
Regulation of Arterial-Venous Differences in Tumor Necrosis Factor Responsiveness of Endothelial Cells by Anatomic Context
Am. J. Pathol.,
April 1, 2008;
172(4):
1088 - 1099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. T. Tuomisto, H. Lumivuori, E. Kansanen, S.-K. Hakkinen, M. P. Turunen, J. V. van Thienen, A. J. Horrevoets, A.-L. Levonen, and S. Yla-Herttuala
Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2
Cardiovasc Res,
April 1, 2008;
78(1):
175 - 184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-H. Woo, T. Shishido, C. McClain, J. H. Lim, J.-D. Li, J. Yang, C. Yan, and J.-i. Abe
Extracellular Signal-Regulated Kinase 5 SUMOylation Antagonizes Shear Stress-Induced Antiinflammatory Response and Endothelial Nitric Oxide Synthase Expression in Endothelial Cells
Circ. Res.,
March 14, 2008;
102(5):
538 - 545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. C. Berk
Atheroprotective Signaling Mechanisms Activated by Steady Laminar Flow in Endothelial Cells
Circulation,
February 26, 2008;
117(8):
1082 - 1089.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wu, C. S. Bohanan, J. C. Neumann, and J. B. Lingrel
KLF2 Transcription Factor Modulates Blood Vessel Maturation through Smooth Muscle Cell Migration
J. Biol. Chem.,
February 15, 2008;
283(7):
3942 - 3950.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. C. W. Groenendijk, K. Van der Heiden, B. P. Hierck, and R. E. Poelmann
The Role of Shear Stress on ET-1, KLF2, and NOS-3 Expression in the Developing Cardiovascular System of Chicken Embryos in a Venous Ligation Model
Physiology,
December 1, 2007;
22(6):
380 - 389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Basu, T. K. Lung, W. Lemsaddek, T. G. Sargent, D. C. Williams Jr, M. Basu, L. C. Redmond, J. B Lingrel, J. L. Haar, and J. A. Lloyd
EKLF and KLF2 have compensatory roles in embryonic {beta}-globin gene expression and primitive erythropoiesis
Blood,
November 1, 2007;
110(9):
3417 - 3425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Rao, L. Yang, G. Garcia-Cardena, and F. W. Luscinskas
Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular Wall
Circ. Res.,
August 3, 2007;
101(3):
234 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Seebach, G. Donnert, R. Kronstein, S. Werth, B. Wojciak-Stothard, D. Falzarano, C. Mrowietz, S. W. Hell, and H.-J. Schnittler
Regulation of endothelial barrier function during flow-induced conversion to an arterial phenotype
Cardiovasc Res,
August 1, 2007;
75(3):
598 - 607.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-J. Chiu, L.-J. Chen, C.-I Lee, P.-L. Lee, D.-Y. Lee, M.-C. Tsai, C.-W. Lin, S. Usami, and S. Chien
Mechanisms of induction of endothelial cell E-selectin expression by smooth muscle cells and its inhibition by shear stress
Blood,
July 15, 2007;
110(2):
519 - 528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. B. Atkins and M. K. Jain
Role of Kruppel-Like Transcription Factors in Endothelial Biology
Circ. Res.,
June 22, 2007;
100(12):
1686 - 1695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. O. Fledderus, J. V. van Thienen, R. A. Boon, R. J. Dekker, J. Rohlena, O. L. Volger, A.-P. J. J. Bijnens, M. J. A. P. Daemen, J. Kuiper, T. J. C. van Berkel, et al.
Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2
Blood,
May 15, 2007;
109(10):
4249 - 4257.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hamik, Z. Lin, A. Kumar, M. Balcells, S. Sinha, J. Katz, M. W. Feinberg, R. E. Gerszten, E. R. Edelman, and M. K. Jain
Kruppel-like Factor 4 Regulates Endothelial Inflammation
J. Biol. Chem.,
May 4, 2007;
282(18):
13769 - 13779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Methe, M. Balcells, M. del Carmen Alegret, M. Santacana, B. Molins, A. Hamik, M. K. Jain, and E. R. Edelman
Vascular bed origin dictates flow pattern regulation of endothelial adhesion molecule expression
Am J Physiol Heart Circ Physiol,
May 1, 2007;
292(5):
H2167 - H2175.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. McMillan, S. N. McMillan, E. Glover, and C. A. Bradfield
2,3,7,8-Tetrachlorodibenzo-p-dioxin Induces Premature Activation of the KLF2 Regulon during Thymocyte Development
J. Biol. Chem.,
April 27, 2007;
282(17):
12590 - 12597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Boon, J. O. Fledderus, O. L. Volger, E. J.A. van Wanrooij, E. Pardali, F. Weesie, J. Kuiper, H. Pannekoek, P. ten Dijke, and A. J.G. Horrevoets
KLF2 Suppresses TGF-{beta} Signaling in Endothelium Through Induction of Smad7 and Inhibition of AP-1
Arterioscler. Thromb. Vasc. Biol.,
March 1, 2007;
27(3):
532 - 539.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. McMillan and C. A. Bradfield
The Aryl hydrocarbon receptor is activated by modified low-density lipoprotein
PNAS,
January 23, 2007;
104(4):
1412 - 1417.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Mitchell, R. Lucas, I. Vojnovic, K. Hasan, J. R. Pepper, and T. D. Warner
Stronger inhibition by nonsteroid anti-inflammatory drugs of cyclooxygenase-1 in endothelial cells than platelets offers an explanation for increased risk of thrombotic events
FASEB J,
December 1, 2006;
20(14):
2468 - 2475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Searles
Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression
Am J Physiol Cell Physiol,
November 1, 2006;
291(5):
C803 - C816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. V. van Thienen, J. O. Fledderus, R. J. Dekker, J. Rohlena, G. A. van IJzendoorn, N. A. Kootstra, H. Pannekoek, and A. J.G. Horrevoets
Shear stress sustains atheroprotective endothelial KLF2 expression more potently than statins through mRNA stabilization
Cardiovasc Res,
November 1, 2006;
72(2):
231 - 240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hirakawa, M. Oike, M. Watanabe, Y. Karashima, and Y. Ito
Pivotal role of integrin {alpha}5{beta}1 in hypotonic stress-induced responses of human endothelium
FASEB J,
October 1, 2006;
20(12):
1992 - 1999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hamik, B. Wang, and M. K. Jain
Transcriptional Regulators of Angiogenesis
Arterioscler. Thromb. Vasc. Biol.,
September 1, 2006;
26(9):
1936 - 1947.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Huddleson, N. Ahmad, and J. B. Lingrel
Up-regulation of the KLF2 Transcription Factor by Fluid Shear Stress Requires Nucleolin
J. Biol. Chem.,
June 2, 2006;
281(22):
15121 - 15128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Dekker, R. A. Boon, M. G. Rondaij, A. Kragt, O. L. Volger, Y. W. Elderkamp, J. C. M. Meijers, J. Voorberg, H. Pannekoek, and A. J. G. Horrevoets
KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium
Blood,
June 1, 2006;
107(11):
4354 - 4363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Ruf
Flow perturbation is linked to endothelial par signaling.
Arterioscler. Thromb. Vasc. Biol.,
May 1, 2006;
26(5):
962 - 964.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Rondaij, R. Bierings, A. Kragt, J. A. van Mourik, and J. Voorberg
Dynamics and Plasticity of Weibel-Palade Bodies in Endothelial Cells
Arterioscler. Thromb. Vasc. Biol.,
May 1, 2006;
26(5):
1002 - 1007.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Lin, A. Hamik, R. Jain, A. Kumar, and M. K. Jain
Kruppel-Like Factor 2 Inhibits Protease Activated Receptor-1 Expression and Thrombin-Mediated Endothelial Activation
Arterioscler. Thromb. Vasc. Biol.,
May 1, 2006;
26(5):
1185 - 1185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gouverneur, J. A. E. Spaan, H. Pannekoek, R. D. Fontijn, and H. Vink
Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx
Am J Physiol Heart Circ Physiol,
January 1, 2006;
290(1):
H458 - H452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Dekker, J. V. van Thienen, J. Rohlena, S. C. de Jager, Y. W. Elderkamp, J. Seppen, C. J.M. de Vries, E. A.L. Biessen, T. J.C. van Berkel, H. Pannekoek, et al.
Endothelial KLF2 Links Local Arterial Shear Stress Levels to the Expression of Vascular Tone-Regulating Genes
Am. J. Pathol.,
August 1, 2005;
167(2):
609 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Parmar, V. Nambudiri, G. Dai, H. B. Larman, M. A. Gimbrone Jr., and G. Garcia-Cardena
Statins Exert Endothelial Atheroprotective Effects via the KLF2 Transcription Factor
J. Biol. Chem.,
July 22, 2005;
280(29):
26714 - 26719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. C.W. Groenendijk, B. P. Hierck, J. Vrolijk, M. Baiker, M. J.B.M. Pourquie, A. C. Gittenberger-de Groot, and R. E. Poelmann
Changes in Shear Stress-Related Gene Expression After Experimentally Altered Venous Return in the Chicken Embryo
Circ. Res.,
June 24, 2005;
96(12):
1291 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Huddleson, N. Ahmad, S. Srinivasan, and J. B Lingrel
Induction of KLF2 by Fluid Shear Stress Requires a Novel Promoter Element Activated by a Phosphatidylinositol 3-Kinase-dependent Chromatin-remodeling Pathway
J. Biol. Chem.,
June 17, 2005;
280(24):
23371 - 23379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. McLaughlin, M. R. Mazzoni, J. H. Cleator, L. Earls, A. L. Perdigoto, J. D. Brooks, J. A. S. Muldowney III, D. E. Vaughan, and H. E. Hamm
Thrombin Modulates the Expression of a Set of Genes Including Thrombospondin-1 in Human Microvascular Endothelial Cells
J. Biol. Chem.,
June 10, 2005;
280(23):
22172 - 22180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Suzuki, K. Aizawa, T. Matsumura, and R. Nagai
Vascular Implications of the Kruppel-Like Family of Transcription Factors
Arterioscler. Thromb. Vasc. Biol.,
June 1, 2005;
25(6):
1135 - 1141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Young, V. Modur, A. A. Teleron, and J. H. Ladenson
Enrichment of Genes in the Aortic Intima That Are Associated With Stratified Epithelium: Implications of Underlying Biomechanical and Barrier Properties of the Arterial Intima
Circulation,
May 10, 2005;
111(18):
2382 - 2390.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Braam, R. de Roos, H. Bluyssen, P. Kemmeren, F. Holstege, J. A. Joles, and H. Koomans
Nitric Oxide-Dependent and Nitric Oxide-Independent Transcriptional Responses to High Shear Stress in Endothelial Cells
Hypertension,
April 1, 2005;
45(4):
672 - 680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Lin, A. Kumar, S. SenBanerjee, K. Staniszewski, K. Parmar, D. E. Vaughan, M. A. Gimbrone Jr, V. Balasubramanian, G. Garcia-Cardena, and M. K. Jain
Kruppel-Like Factor 2 (KLF2) Regulates Endothelial Thrombotic Function
Circ. Res.,
March 18, | |
