IGF-1 Therapy Improves Muscle Size and Function in Experimental Peripheral Arterial Disease.
IGF-1 Therapy Improves Muscle Size and Function in Experimental Peripheral Arterial Disease.
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DOI：
10.1016/j.jacbts.2022.12.006
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发表时间：
2023-06
影响因子：
9.7
通讯作者：
Ryan, Terence E.
中科院分区：
文献类型：
--
作者：
Dong, Gengfu;Moparthy, Chatick;Thome, Trace;Kim, Kyoungrae;Yue, Feng;Ryan, Terence E.
ScAAV9基因疗法可以被输送到严重缺血的小鼠肢体，并在其中产生强劲的转基因表达，而不会对灌注恢复或肌肉健康/功能产生不利影响。用scAAV9-IGF-1治疗后肢缺血的雄性和雌性后肢缺血小鼠的肌肉大小和力量均显著改善。观察到scAAV9-IGF-1的疗效差异，雌性小鼠在肌肉收缩功能方面表现出比雄性小鼠更大的改善。IGF-1介导的肌肉功能改善发生在肢体血流恢复或毛细血管密度没有改变的情况下。下肢外周动脉疾病(PAD)的患病率有所增加，但治疗进展仍然停滞不前。骨骼肌的健康和功能与PAD患者的生活质量和医疗结果密切相关。使用PAD的啮齿动物模型，本研究表明，胰岛素样生长因子(IGF)-1治疗缺血肢体显著增加肌肉大小和力量，而不改善肢体血流动力学。有趣的是，IGF1治疗在雌性小鼠中的效果比在雄性小鼠中更大，这突显了在实验性PAD治疗中仔细检查性别依赖效应的必要性。
scAAV9 gene therapies can be delivered to, and produce robust transgene expression in, the critically ischemic mouse limb without adverse impact on perfusion recovery or muscle health/function. Treatment of the ischemic limb with scAAV9–IGF-1 significantly improved muscle size and strength in male and female mice with hindlimb ischemia. Differences in the efficacy of scAAV9–IGF-1 were observed, with female mice displaying greater improvements in muscle contractile function than male mice. IGF-1-mediated improvements in muscle function occurred without changes in limb perfusion recovery or capillary density. Lower-extremity peripheral arterial disease (PAD) has increased in prevalence, yet therapeutic development has remained stagnant. Skeletal muscle health and function has been strongly linked to quality of life and medical outcomes in patients with PAD. Using a rodent model of PAD, this study demonstrates that treatment of the ischemic limb with insulin-like growth factor (IGF)-1 significantly increases muscle size and strength without improving limb hemodynamics. Interestingly, the effect size of IGF1 therapy was larger in female mice than in male mice, highlighting the need to carefully examine sex-dependent effects in experimental PAD therapies.
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外周缺血的多效性基因治疗：全长和截短基因变异的评估。
影响因子：
3.7
作者：
Fang Q;Mok PY;Thomas AE;Haddad DJ;Saini SA;Clifford BT;Kapasi NK;Danforth OM;Usui M;Ye W;Luu E;Sharma R;Bartel MJ;Pathmanabhan JA;Ang AA;Sievers RE;Lee RJ;Springer ML
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影响因子：
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影响因子：
168.9
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通讯作者：
Criqui, Michael H.
DOI：
10.1093/gerona/gls102
发表时间：
2012-06-01
影响因子：
5.1
作者：
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通讯作者：
Delafontaine, Patrice