Retracted: RhoA activation and interaction with Caveolin-1 are critical for pressure-induced myogenic tone in rat mesenteric resistance arteries
Authors: Christophe Heymes
Xavier Loyer
Jean-Luc Balligand
Pierre Pacaud
Kevin Retailleau
Caroline Dubroca
Daniel Henrion
Olivier Feron
Gervaise Loirand
Bernard I Lévy
Journal: Cardiovascular Research (2007)
Discipline: CLINICAL MEDICINE
Keywords: Myogenic tone; RhoA; caveolin-1; pressure-induced tone; Rho-kinase
Affiliations: Centre de Recherche Cardiovasculaire Lariboisière, INSERM U689, Paris, France., Centre de Recherche Cardiovasculaire Lariboisière, INSERM U689, Paris, France, CNRS UMR 6214, Angers, France, INSERM U771, Angers, France, Institut du Thorax, INSERM Unit 533, Nantes, France, Unit of Pharmacology and Therapeutics UCL-FATH5349, Brussels, Belgium

Abstract:  Objective: Myogenic tone, which has a major role in the regulation of local blood flow, refers to the ability of vascular smooth muscle to adapt its contractility to changes in transmural pressure. Although Rho-kinase is involved in myogenic tone, the pathway involved remains unclear, especially concerning translocation to the plasma membrane and activation of RhoA. As caveolae have a key role in the signal transduction of membrane-bound proteins, we tested the hypothesis that RhoA might be activated by pressure and that its activation might involve caveolin-1, which has been shown to be involved in vascular functions. Methods: Myogenic tone was studied in isolated rat mesenteric resistance arteries (118+/-15 microm internal diameter with a pressure of 75 mmHg) submitted to pressure steps (25, 75, and 150 mmHg). Pharmacological blockade of caveolae or RhoA-Rho-kinase pathway was assessed by confocal microscopy in pressurized arteries to analyze protein co-localization and by co-immunoprecipitation in order to confirm protein interactions. Caveolin-1-deficient mice were used to confirm the role of the protein in myogenic tone. Results: Pressure-induced myogenic tone was significantly reduced by RhoA inactivation with TAT-C3 (90.5% inhibition at 150 mmHg) and by the Rho-kinase inhibitor Y27632 (91.8% inhibition at 150 mmHg). In arteries pressurized at 150 mmHg, RhoA was localized to the plasma membrane (localization by confocal microscopy and increased quantity of RhoA in the membrane fraction after protein extraction). Thus, translocation of RhoA to the plasma membrane was associated with pressure-induced tone. In addition, caveolae disruption with methyl-beta-cyclodextrin reduced myogenic tone by 66% at 150 mmHg. Further, myogenic tone was significantly reduced to 24% of control in caveolin-1-deficient mice (active tone was 32.3+/-2.8 microm and 9.1+/-3.7 microm in +/+ and -/- mice, respectively, n = 5 per group), suggesting a key role of caveolin-1 in myogenic tone. Finally, RhoA and caveolin-1 co-immunoprecipitation and co-localization significantly increased when myogenic tone developed at 150 mmHg (co-localization showed 26+/-13% merging at 25 mmHg versus 97+/-21% at 150 mmHg, n = 5). Co-immunoprecipitation was prevented by TAT-C3 and by methyl beta-cyclodextrin. Conclusion: RhoA activation is critical for the development of myogenic tone in resistance arteries. This activation induced translocation of RhoA to the plasma membrane within caveolae, where the interaction of RhoA with caveolin-1 leads selectively to the activation of a Rho-kinase-dependent force development. 

Retracted: No

PubPeer comments:
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 Figure 4. Clarification. ![file] , 
 This article has an Editorial Expression of Concern https: academic.oup.com cardiovascres advance-article doi 10.1093 cvr cvaa104 5824087  The Editorial Office was alerted (14th October 2019) by a reader to concerns about the data presented in Figure 4 of the above mentioned paper. In line with COPE guidance, the Cardiovascular Research Editorial Office made contact with the corresponding author of the manuscript. The corresponding author confirmed that an error had been made in collating the representative western blots shown in Figure 4. However, the authors were unable to retrieve the original blots. The matter was assessed by the ESC Journal Family Ethics Committee and an external independent reviewer was appointed. The outcome of this process was that the authors must experimentally confirm the validity of the data in question. The Editors of Cardiovascular Research have decided to place an expression of concern related to this paper to inform readers appropriately, whilst we wait for the experiments to be performed. , 
 Retraction note: Caroline Dubroca, Xavier Loyer, Kevin Retailleau, Gervaise Loirand, Pierre Pacaud, Olivier Feron, Jean-Luc Balligand, Bernard I. Lu00e9vy, Christophe Heymes, Daniel Henrion. An expression of concern was issued by the Journal following concerns raised regarding Figure 4. The authors have been unable to experimentally confirm the validity of the data in question, and the editors have agreed to retract this article. This conclusion has been reviewed and approved by the ESC Journals Family Ethics Committee. https: academic.oup.com cardiovascres advance-article doi 10.1093 cvr cvab219 6314361?login=true ,