Systematic Interrogation of Angiogenesis in the Ischemic Mouse Hind Limb: Vulnerabilities and Quality Assurance.
Systematic Interrogation of Angiogenesis in the Ischemic Mouse Hind Limb: Vulnerabilities and Quality Assurance.
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DOI：
10.1161/atvbaha.120.315028
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Pickering JG
中科院分区：
文献类型：
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作者：
Lee JJ;Arpino JM;Yin H;Nong Z;Szpakowski A;Hashi AA;Chevalier J;O'Neil C;Pickering JG
文本中提供了补充数字内容。在将小鼠后肢缺血的临床前研究转化为外周动脉疾病患者的益处方面，几乎没有成功。使用系统的策略，我们试图定义在小鼠后肢缺血损伤和血管生成景观，并确定是否已发表的研究，迄今已使用的分析策略与这些数据一致。根据肌纤维核的丢失或集中，从12周龄C57 BL/6小鼠的22个不同的后肢肌肉和33个肌肉区域生成缺血性损伤的地图。基于CD（分化簇）31阳性毛细血管内容物类似地绘制血管生成。33个肌肉区域中只有10个显示出持续的肌肉损伤，其中远侧前后肢肌肉最容易受伤。血管生成呈片状，仅与再生肌肉区（中央核）相关。在正常肌肉、坏死肌肉或损伤边缘区未观察到血管生成。对小鼠后肢血管生成研究的系统性综述确定了5147篇独特的出版物，其中509篇符合分析的合格标准。这些分析的手稿中只有7%评价了后肢远端前肌的血管生成，只有15%始终检查了肌肉再生区的血管生成。在12周的C57 BL/6小鼠中，股动脉切除后的血管生成仅在肌肉再生区进行。迄今为止，只有少数研究分析了可证明再生肌肉区域或高可能性区域的血管生成。质量保证标准，告知地图集和映射数据在这里，可以增加数据的可靠性，并有可能帮助翻译小鼠后肢缺血研究病人护理。
Supplemental Digital Content is available in the text. There has been little success in translating preclinical studies of mouse hind limb ischemia into benefit for patients with peripheral artery disease. Using systematic strategies, we sought to define the injury and angiogenesis landscapes in mice subjected to hind limb ischemia and ascertain whether published studies to date have used an analysis strategy concordant with these data. Maps of ischemic injury were generated from 22 different hind limb muscles and 33 muscle territories in 12-week-old C57BL/6 mice, based on loss or centralization of myofiber nuclei. Angiogenesis was similarly mapped based on CD (cluster of differentiation) 31–positive capillary content. Only 10 of 33 muscle territories displayed consistent muscle injury, with the distal anterior hind limb muscles most reliably injured. Angiogenesis was patchy and exclusively associated with zones of regenerated muscle (central nuclei). Angiogenesis was not observed in normal appearing muscle, necrotic muscle, or injury border zones. Systematic review of mouse hind limb angiogenesis studies identified 5147 unique publications, of which 509 met eligibility criteria for analysis. Only 7% of these analyzed manuscripts evaluated angiogenesis in distal anterior hind limb muscles and only 15% consistently examined for angiogenesis in zones of muscle regeneration. In 12-week C57BL/6 mice, angiogenesis postfemoral artery excision proceeds exclusively in zones of muscle regeneration. Only a minority of studies to date have analyzed angiogenesis in regions of demonstrably regenerating muscle or in high-likelihood territories. Quality assurance standards, informed by the atlas and mapping data herein, could augment data reliability and potentially help translate mouse hind limb ischemia studies to patient care.