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肌肉对抗骨肌肉功能障碍和心力衰竭中的运动不耐受性,使用保存的喷射分数

Eng Leng Saw¹, Louis Dominic Werner¹, Hannah L Cooper¹

¹Department of Medicine, Whitaker Cardiovascular Institute, Boston University Chobanian & Avedisian School of Medicine, MA (E.L.S., L.D.W., H.L.C., D.R.P., M.V.-M., F.S.).

Circulation. Heart failure

|May 13, 2025

概括

肌肉素的使用改善了骨肌肉功能和心力衰竭中的运动能力,并保留了喷射分数 (HFpEF). 这种myokine增强了氧化能力,为HFpEF相关的运动不耐受提供了潜在的治疗标.

科学领域:

心血管研究研究心血管研究
骨肌肉生理学骨肌肉生理学
代谢性疾病代谢性疾病

背景情况:

在心力衰竭中,运动不耐受与保存的喷射分数 (HFpEF) 与骨肌肉 (SkM) 功能障碍和氧化能力降低有关.
肌素,如肌肉素,由SkM分泌以维持氧化能力并影响尿素 (NP) 和过氧体增殖器激活的受体-γ联合激活器-1αα (PGC-1α) 信号传递.

研究的目的:

在HFpEF的背景下,研究肌肉在骨肌肉功能障碍中的作用.
评估外源肌肉在改善与HFpEF相关的骨肌肉损伤和运动不耐受性方面的治疗潜力.

主要方法:

使用小鼠模型 (SAUNA) 诱导HFpEF,在干预期内给出异源肌肉素.
对血液和骨肌肉 (小鼠的soleus,HFpEF患者的vastus lateralis) 进行分子分析,以评估信号通路和肌肉纤维特征.

主要成果:

HFpEF与肌肉的增加和循环氨酸单酸和PGC-1α水平的降低有关,这表明NP信号受损.
在HFpEF小鼠中,外源性肌的使用增强了NP信号传递,促进了向耐力导向肌肉纤维 (类型-2A到类型-1) 的转变,并改善了氧化能力标志物.
肌肉治疗改善了HFpEF小鼠的功能和运动能力,并减轻了心脏缩,而不会对血压或透气功能产生不良影响.

结论:

肌肉在HFpEF中对骨肌肉和心脏功能产生有益影响,可能是通过增强SkM的氧化能力.
这些发现表明肌肉素是提高HFpEF患者运动能力的潜在治疗剂,需要进一步的临床研究.

关键词:

运动耐受性运动耐受性心脏衰竭是因为心脏衰竭.肌肉,骨和骨的组织.肌痛的原因是myokines.这是一种天然尿素.

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