HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/4/H1720    most recent 00344.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (52) Citing Articles via Google Scholar Google Scholar Articles by Rizzo, V. Articles by Davies, P. F. Search for Related Content PubMed PubMed Citation Articles by Rizzo, V. Articles by Davies, P. F.

Recruitment of endothelial caveolae into mechanotransduction pathways by flow conditioning in vitro

¹Center for Cardiovascular Science, Albany Medical College, Albany 12208; ²Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180; ³Vascular Biology and Angiogenesis Program, Sidney Kimmel Cancer Center, San Diego, California 92121; and ⁴Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Submitted 18 April 2002 ; accepted in final form 14 June 2003

The luminal surface of rat lung microvascular endothelial cells in situ is sensitive to changing hemodynamic parameters. Acute mechanosignaling events initiated in response to flow changes in perfused lung microvessels are localized within specialized invaginated microdomains called caveolae. Here we report that chronic exposure to shear stress alters caveolin expression and distribution, increases caveolae density, and leads to enhanced mechanosensitivity to subsequent changes in hemodynamic forces within cultured endothelial cells. Flow-preconditioned cells expressed a fivefold increase in caveolin (and other caveolar-residing proteins) at the luminal surface compared with no-flow controls. The density of morphologically identifiable caveolae was enhanced sixfold at the luminal cell surface of flow-conditioned cells. Laminar shear stress applied to static endothelial cultures (flow step of 5 dyn/cm²), enhanced the tyrosine phosphorylation of luminal surface proteins by 1.7-fold, including caveolin-1 by 1.3-fold, increased Ser¹¹⁷⁹ phosphorylation of endothelial nitric oxide synthase (eNOS) by 2.6-fold, and induced a 1.4-fold activation of mitogen-activated protein kinases (ERK1/2) over no-flow controls. The same shear step applied to endothelial cells preconditioned under 10 dyn/cm² of laminar shear stress for 6 h and induced a sevenfold increase of total phosphotyrosine signal at the luminal endothelial cell surface enhanced caveolin-1 tyrosine phosphorylation 5.8-fold and eNOS phosphorylation by 3.3-fold over static control values. In addition, phosphorylated caveolin-1 and eNOS proteins were preferentially localized to caveolar microdomains. In contrast, ERK1/2 activation was not detected in conditioned cells after acute shear challenge. These data suggest that cultured endothelial cells respond to a sustained flow environment by directing caveolae to the cell surface where they serve to mediate, at least in part, mechanotransduction responses.

shear stress; endothelial cells

This article has been cited by other articles:

				J. E. Testa, A. Chrastina, P. Oh, Y. Li, H. Witkiewicz, M. Czarny, T. Buss, and J. E. Schnitzer Immunotargeting and cloning of two CD34 variants exhibiting restricted expression in adult rat endothelia in vivo Am J Physiol Lung Cell Mol Physiol, August 1, 2009; 297(2): L251 - L262. [Abstract] [Full Text] [PDF]

				J.-L. Balligand, O. Feron, and C. Dessy eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues Physiol Rev, April 1, 2009; 89(2): 481 - 534. [Abstract] [Full Text] [PDF]

				P. M. Haram, O. J. Kemi, S. J. Lee, M. O. Bendheim, Q. Y. Al-Share, H. L. Waldum, L. J. Gilligan, L. G. Koch, S. L. Britton, S. M. Najjar, et al. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity Cardiovasc Res, March 1, 2009; 81(4): 723 - 732. [Abstract] [Full Text] [PDF]

				C. Hahn and M. A. Schwartz The Role of Cellular Adaptation to Mechanical Forces in Atherosclerosis Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2101 - 2107. [Abstract] [Full Text] [PDF]

				F. Peng, B. Zhang, D. Wu, A. J. Ingram, B. Gao, and J. C. Krepinsky TGF{beta}-induced RhoA activation and fibronectin production in mesangial cells require caveolae Am J Physiol Renal Physiol, July 1, 2008; 295(1): F153 - F164. [Abstract] [Full Text] [PDF]

				D. Hong, D. Jaron, D. G. Buerk, and K. A. Barbee Transport-dependent calcium signaling in spatially segregated cellular caveolar domains Am J Physiol Cell Physiol, March 1, 2008; 294(3): C856 - C866. [Abstract] [Full Text] [PDF]

				S. Belmonte and M. Morad 'Pressure-flow'-triggered intracellular Ca2+ transients in rat cardiac myocytes: possible mechanisms and role of mitochondria J. Physiol., March 1, 2008; 586(5): 1379 - 1397. [Abstract] [Full Text] [PDF]

				S. Albinsson, I. Nordstrom, K. Sward, and P. Hellstrand Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall Am J Physiol Cell Physiol, January 1, 2008; 294(1): C271 - C279. [Abstract] [Full Text] [PDF]

				S. A. Predescu, D. N. Predescu, and A. B. Malik Molecular determinants of endothelial transcytosis and their role in endothelial permeability Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L823 - L842. [Abstract] [Full Text] [PDF]

				S. J. Nixon, A. Carter, J. Wegner, C. Ferguson, M. Floetenmeyer, J. Riches, B. Key, M. Westerfield, and R. G. Parton Caveolin-1 is required for lateral line neuromast and notochord development J. Cell Sci., July 1, 2007; 120(13): 2151 - 2161. [Abstract] [Full Text] [PDF]

				F. Shi, Y.-J. Chiu, Y. Cho, T. A. Bullard, M. Sokabe, and K. Fujiwara Down-regulation of ERK but not MEK phosphorylation in cultured endothelial cells by repeated changes in cyclic stretch Cardiovasc Res, March 1, 2007; 73(4): 813 - 822. [Abstract] [Full Text] [PDF]

				F. Peng, D. Wu, A. J. Ingram, B. Zhang, B. Gao, and J. C. Krepinsky RhoA Activation in Mesangial Cells by Mechanical Strain Depends on Caveolae and Caveolin-1 Interaction J. Am. Soc. Nephrol., January 1, 2007; 18(1): 189 - 198. [Abstract] [Full Text] [PDF]

				A. Makino, E. R. Prossnitz, M. Bunemann, J. M. Wang, W. Yao, and G. W. Schmid-Schonbein G protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1633 - C1639. [Abstract] [Full Text] [PDF]

				L. H. Romer, K. G. Birukov, and J. G.N. Garcia Focal Adhesions: Paradigm for a Signaling Nexus Circ. Res., March 17, 2006; 98(5): 606 - 616. [Abstract] [Full Text] [PDF]

				C.-F. Lam, T. E. Peterson, D. M. Richardson, A. J. Croatt, L. V. d'Uscio, K. A. Nath, and Z. S. Katusic Increased blood flow causes coordinated upregulation of arterial eNOS and biosynthesis of tetrahydrobiopterin Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H786 - H793. [Abstract] [Full Text] [PDF]

				C. Cheng, R. van Haperen, M. de Waard, L. C. A. van Damme, D. Tempel, L. Hanemaaijer, G. W. A. van Cappellen, J. Bos, C. J. Slager, D. J. Duncker, et al. Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique Blood, December 1, 2005; 106(12): 3691 - 3698. [Abstract] [Full Text] [PDF]

				Z. Bagi, J. A. Frangos, J.-C. Yeh, C. R. White, G. Kaley, and A. Koller PECAM-1 Mediates NO-Dependent Dilation of Arterioles to High Temporal Gradients of Shear Stress Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1590 - 1595. [Abstract] [Full Text] [PDF]

				M. Milkiewicz, O. Hudlicka, M. D. Brown, and H. Silgram Nitric oxide, VEGF, and VEGFR-2: interactions in activity-induced angiogenesis in rat skeletal muscle Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H336 - H343. [Abstract] [Full Text] [PDF]

				C. Radel and V. Rizzo Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H936 - H945. [Abstract] [Full Text] [PDF]

				M. Czarny and J. E. Schnitzer Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1344 - H1352. [Abstract] [Full Text] [PDF]

				J.-P. Gratton, P. Bernatchez, and W. C. Sessa Caveolae and Caveolins in the Cardiovascular System Circ. Res., June 11, 2004; 94(11): 1408 - 1417. [Abstract] [Full Text] [PDF]

				J. T. Ferraro, M. Daneshmand, R. Bizios, and V. Rizzo Depletion of plasma membrane cholesterol dampens hydrostatic pressure and shear stress-induced mechanotransduction pathways in osteoblast cultures Am J Physiol Cell Physiol, April 1, 2004; 286(4): C831 - C839. [Abstract] [Full Text] [PDF]