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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1579.)
© 2002 American Heart Association, Inc.

Vascular Biology

Excessive Microvascular Adaptation to Changes in Blood Flow in Mice Lacking Gene Encoding for Desmin

Laurent Loufrani; Zhenlin Li; Bernard I. Lévy; Denise Paulin; Daniel Henrion

From the Institut National de la Santé et de la Recherche Médicale (INSERM) U 541 (L.L., D.H.), IFR Circulation-Paris-Nord; the Department of Physiology (B.I.L.), AP-HP-Hôpital Lariboisière; and the Laboratoire de Biologie Moléculaire de la Différentiation (Z.L., D.P.), Paris VII University, Paris, France.

Correspondence to D. Henrion, PhD, INSERM U 541, 41 Bd de la Chapelle, 75475 Paris, Cedex 10, France. E-mail daniel.henrion{at}inserm.lrb.ap-hop-paris.fr

Objective— Desmin, an intermediate filament, has a key role in the integrity of myocytes, and its absence induces cardiomyopathies. Mice lacking desmin (Des-/- group) exhibit microvascular dysfunction leading to smooth muscle hyporeactivity. We investigated the effect of the absence of desmin in mice (Des-/- mice versus Des+/+ mice) on the adaptation of mesenteric arteries to changes in blood flow.

Methods and Results— With the use of selective ligations of second-order mesenteric arteries, blood flow was either diminished (low flow [LF]) or elevated (high flow [HF]); respective LF to HF values were 136±18 to 206±29 µL/min for Des+/+ mice and 119±14 to 189±24 µL/min for Des-/-mice in daughter arteries. Two weeks after ligation, arteries were mounted in an arteriograph, allowing the measurement of diameter under controlled conditions of pressure and flow. In HF arteries, diameter changes in response to increases in pressure were higher in Des-/- mice than in Des+/+ mice. Conversely, in LF arteries, diameter was lower in Des-/- mice. Flow-dependent dilation was higher in HF arteries and lower in LF arteries than in control arteries. This adaptation was lower in Des-/- mice than in Des+/+ mice (11.6±3.1% versus 25.5±4.8% dilation, respectively). Endothelial NO synthase expression increased in HF arteries in both strains.

Conclusions— These findings provide a demonstration of the role of the intermediate filament desmin in microvascular remodeling. This dysfunction might take place in desmin-related myopathies.

Key Words: vascular blood flow • flow-dependent dilation • endothelium • smooth muscle • myopathies

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