Straino Stefania, Germani Antonia, Di Carlo Anna, Porcelli Daniele, De Mori Roberta, Mangoni Antonella, Napolitano Monica, Martelli Fabio, Biglioli Paolo, Capogrossi Maurizio C
Laboratorio di Biologia Vascolare e Terapia Genica, Centro Cardiologico I, Monzino, IRCCS, Milan, Italy.
Circulation. 2004 Nov 23;110(21):3341-8. doi: 10.1161/01.CIR.0000147776.50787.74. Epub 2004 Nov 15.
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.
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.
These results demonstrate that arteriogenesis is enhanced in mdx mice both after ischemia and skin wounding and in response to growth factors.
杜氏肌营养不良症（DMD）患者和mdx小鼠体内缺乏功能性肌营养不良蛋白，导致进行性肌肉变性，伴有坏死、纤维化和炎症。由于血管供应在组织修复中起关键作用，我们研究了mdx小鼠的新血管发育是否发生改变。
在股动脉解剖的后肢缺血模型中，通过激光多普勒成像测量，mdx小鼠的后肢灌注（0.67±0.26）高于野生型（WT）小鼠（0.33±0.18，P<0.03）。与这些数据一致，mdx小鼠的小动脉长度密度（13.6±8.4 mm/mm³）与WT小鼠（7.8±4.6 mm/mm³，P<0.03）相比显著增加。相反，两种基因型小鼠的毛细血管密度没有差异。增强的再生反应并不局限于缺血骨骼肌，因为在伤口愈合试验中，mdx小鼠与WT小鼠相比显示出加速的伤口闭合率。此外，在皮下注射含碱性成纤维细胞生长因子的基质胶栓的血管生成试验中，mdx小鼠（46.9±14.7 mm/mm³）的小动脉长度密度高于WT小鼠（19.5±5.8 mm/mm³，P<0.001）。最后，mdx小鼠血清在体外比WT血清更有效地维持内皮细胞衍生管状结构的形成。
这些结果表明，mdx小鼠在缺血和皮肤损伤后以及对生长因子的反应中，动脉生成均增强。
