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(Circulation Research. 2007;101:7.)
© 2007 American Heart Association, Inc.

Editorials

Endogenous RhoA Inhibitor Protects Endothelial Barrier

Geerten P. van Nieuw Amerongen, Victor W.M. van Hinsbergh

From the Department of Physiology (G.P.v.N.A., V.W.M.v.H.), Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, Netherlands.

Correspondence to Victor W.M. van Hinsbergh, PhD, Department of Physiology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. E-mail v.vanhinsbergh@vumc.nl

See related article, pages 50–58

Key Words: endothelial permeability • acute respiratory distress syndrome • sepsis • RhoA • RhoGDI

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Vascular leakage is a hallmark of many, often life-threatening, inflammatory diseases, and contributes to disease severity in disorders such as sepsis, cancer, diabetes, and atherosclerosis.¹ Despite the tremendous medical importance of vascular leakage, few specific therapies are available today to counteract it, and current therapies often fail to do so.² This is in part because the in vivo molecular targets are incompletely identified, although a wealth of data obtained from in vitro studies is available on signal transduction pathways that regulate vascular permeability.^3,4 Interestingly, among various new agents that potentially reduce endothelial hyperpermeability, the cholesterol-lowering statin drugs have been proposed to reduce vascular leakage by means of their inhibitory effects on RhoA proteins.^5,6

In the current issue of Circulation Research Gorovoy et al provide an elegant proof-of-principle that increased RhoA activity results in vascular hyperpermeability in vivo.⁷ They show that elevation of RhoA activity by deletion of one of its inhibitory proteins, RhoGDI, causes a loss of endothelial junctional integrity and decrease in vascular barrier function.

Rho GTPases, particularly RhoA, Rac-1 and cdc42 have received much attention as key regulators of cell shape, movement and proliferation. In vitro studies have shown that the balance of activities of these small G proteins determines the status of endothelial barrier⁸: Cdc42 enhancing recovery of a disturbed barrier,⁹ Rac-1 being required for establishing a tight barrier,⁸ and RhoA being involved in inducing endothelial hyperpermeability by various stimuli, such as thrombin, VEGF, angiopoietin-2 and LPA (see Figure).^10–12 Similarly, these Rho GTPases are acting . . . [Full Text of this Article]

Related Article:

RhoGDI-1 Modulation of the Activity of Monomeric RhoGTPase RhoA Regulates Endothelial Barrier Function in Mouse Lungs

Matvey Gorovoy, Radu Neamu, Jiaxin Niu, Stephen Vogel, Dan Predescu, Jun Miyoshi, Yoshimi Takai, Vidisha Kini, Dolly Mehta, Asrar B. Malik, and Tatyana Voyno-Yasenetskaya
Circ. Res. 2007 101: 50-58. [Abstract] [Full Text] [PDF]

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