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(Circulation. 2004;110:3341-3348.)
© 2004 American Heart Association, Inc.

Vascular Medicine

Enhanced Arteriogenesis and Wound Repair in Dystrophin-Deficient mdx Mice

Stefania Straino, BS^*; Antonia Germani, PhD^*; Anna Di Carlo, PhD; Daniele Porcelli, MSc; Roberta De Mori, MSc; Antonella Mangoni, BS; Monica Napolitano, MD; Fabio Martelli, PhD; Paolo Biglioli, MD; Maurizio C. Capogrossi, MD

From the Laboratorio di Biologia Vascolare e Terapia Genica, Centro Cardiologico I, Monzino, IRCCS, Milan (S.S., A.G., A.D.C., A.M., P.B.), and the Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’Immacolata, IRCCS, Rome (D.P., R.D.M., M.N., F.M., M.C.C.), Italy.

Correspondence to Antonia Germani, Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’Immacolata-IDI, Via Monti di Creta 104, 00167 Rome, Italy. E-mail a.germani{at}idi.it

Received April 16, 2004; revision received September 9, 2004; accepted September 24, 2004.

Background— The absence of functional dystrophin in Duchenne muscular dystrophy (DMD) patients and in mdx mice results in progressive muscle degeneration associated with necrosis, fibrosis, and inflammation. Because vascular supply plays a key role in tissue repair, we examined whether new blood vessel development was altered in mdx mice.

Methods and Results— In a model of hindlimb ischemia on femoral artery dissection, hindlimb perfusion, measured by laser Doppler imaging, was higher in mdx mice (0.67±0.26) than in wild-type (WT) mice (0.33±0.18, P<0.03). In keeping with these data, a significant increase in arteriole length density was found in mdx mice (13.6±8.4 mm/mm³) compared with WT mice (7.8±4.6 mm/mm³, P<0.03). Conversely, no difference was observed in capillary density between mice of the 2 genotypes. The enhanced regenerative response was not limited to ischemic skeletal muscle, because in a wound-healing assay, mdx mice showed an accelerated wound closure rate compared with WT mice. Moreover, a vascularization assay in Matrigel plugs containing basic fibroblast growth factor injected subcutaneously revealed an increased length density of arterioles in mdx (46.9±14.7 mm/mm³) versus WT mice (19.5±5.8 mm/mm³, P<0.001). Finally, serum derived from mdx mice sustained formation of endothelium-derived tubular structures in vitro more efficiently than WT serum.

Conclusions— These results demonstrate that arteriogenesis is enhanced in mdx mice both after ischemia and skin wounding and in response to growth factors.

Key Words: muscles • genetics • vessels

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Ahlke Heydemann and Elizabeth M. McNally
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