Published Online
on November 15, 2004

A more recent version of this article appeared on November 23, 2004

This Article Full Text (PDF) Data Supplement All Versions of this Article: 110/21/3341    most recent 01.CIR.0000147776.50787.74v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Straino, S. Articles by Capogrossi, M. C. Search for Related Content PubMed PubMed Citation Articles by Straino, S. Articles by Capogrossi, M. C. Related Collections Angiogenesis Other Vascular biology Related Article

Submitted on April 16, 2004
Revised on September 9, 2004
Accepted on September 24, 2004

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, and 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.

^* To whom correspondence should be addressed. E-mail: a.germani{at}idi.it.

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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