(Circulation. 2001;103:864.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Flow (Shear Stress)–Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin
From the Institut National de la Santé et de la Recherche Médicale (INSERM) U 541, IFR6, Université Paris VII; Department of Physiology, AP-HP-Hôpital Lariboisière (B.I.L.); and Department of Molecular Biology, Institut Pasteur (I.B.), Paris, France.
Correspondence to D. Henrion, PhD, INSERM U 541, Hôpital Lariboisiere, 41 Blvd de la Chapelle, 75475 Paris, Cedex 10, France. E-mail daniel.henrion{at}inserm.lrb.ap-hop-paris.fr
Background—Dystrophin has a key role in striated muscle mechanotransduction of physical forces. Although cytoskeletal elements play a major role in the mechanotransduction of pressure and flow in vascular cells, the role of dystrophin in vascular function has not yet been investigated. Thus, we studied endothelial and muscular responses of arteries isolated from mice lacking dystrophin (mdx mice).
Methods and Results—Carotid and mesenteric resistance arteries 120 µm in diameter were isolated and mounted in vitro in an arteriograph to control intraluminal pressure and flow. Blood pressure was not affected by the absence of dystrophin. Pressure-induced (myogenic), phenylephrine-induced, and KCl-induced forms of tone were unchanged. Flow (shear stress)–induced dilation in arteries isolated from mdx mice was decreased by 50% to 60%, whereas dilation to acetylcholine or sodium nitroprusside was unaffected. NG-nitro-L-arginine methyl ester–sensitive flow dilation was also decreased in arteries from mdx mice. Thus, the absence of dystrophin was associated with a defect in signal transduction of shear stress. Dystrophin was present in vascular endothelial and smooth muscle cells, as shown by immunolocalization, and localized at the level of the plasma membrane, as seen by confocal microscopy of perfused isolated arteries.
Conclusions—This is the first functional study of arteries lacking the gene for dystrophin. Vascular reactivity was normal, with the exception of flow-induced dilation. Thus, dystrophin could play a specific role in shear-stress mechanotransduction in arterial endothelial cells. Organ damage in such diseases as Duchenne dystrophy might be aggravated by such a defective arterial response to flow.
Key Words: endothelium • genes • dystrophin
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