Skeletal muscle phenotypic switching in heart failure with preserved ejection fraction.
Skeletal muscle phenotypic switching in heart failure with preserved ejection fraction.
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DOI：
10.3389/fcvm.2022.1016452
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发表时间：
2022
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
骨骼肌（SkM）表型转换与射血分数保留性心力衰竭（HFpEF）的运动不耐受相关。HFpEF患者1型氧化纤维减少，线粒体功能障碍，表明氧化能力受损。SAUNA（SAlty饮用水/单侧肾切除术/醛固酮）小鼠常用于HFpEF临床前研究，并显示心脏、肺、肾和白色脂肪组织损伤。然而，SkM（特别是氧化为主的比目鱼肌）尚未在该临床前HFpEF模型中描述。我们试图描述HFpEF SAUNA小鼠比目鱼肌骨骼肌的特征，并研究其翻译潜力。通过单侧肾切除、渗透泵植入法注入d-醛固酮或生理盐水（Sham）诱导HFpEF，并给予1%NaCl饮用水4周。对小鼠实施安乐死，并收集氧化优势比目鱼肌。我们检查了纤维成分、纤维横截面积、毛细血管密度和纤维化。还进行了分子分析。为了研究该模型的临床相关性，对HFpEF患者的氧化优势股外侧肌进行活检，并检查线粒体氧化磷酸化、血管、纤维化和炎症的分子变化。组织学分析表明，与假手术组相比，HFpEF小鼠比目鱼肌中氧化纤维的丰度减少，2A型纤维萎缩，毛细血管密度降低，纤维化面积增加。还观察到感兴趣的靶点表达，如线粒体氧化磷酸化基因减少、VEGF-α增加和炎症反应升高。HFpEF小鼠中的组织学和分子变化与HFpEF患者的氧化主导型SkM中观察到的变化一致且相当。HFpEF SAUNA模型概括了在HFpEF患者中观察到的SkM表型转换。该模型适用于HFpEF中SkM表型转换的研究。
Skeletal muscle (SkM) phenotypic switching is associated with exercise intolerance in heart failure with preserved ejection fraction (HFpEF). Patients with HFpEF have decreased type-1 oxidative fibers and mitochondrial dysfunction, indicative of impaired oxidative capacity. The SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) mice are commonly used in HFpEF pre-clinical studies and demonstrate cardiac, lung, kidney, and white adipose tissue impairments. However, the SkM (specifically the oxidative-predominant, soleus muscle) has not been described in this preclinical HFpEF model. We sought to characterize the soleus skeletal muscle in the HFpEF SAUNA mice and investigate its translational potential. HFpEF was induced in mice by uninephrectomy, d-aldosterone or saline (Sham) infusion by osmotic pump implantation, and 1% NaCl drinking water was given for 4 weeks. Mice were euthanized, and the oxidative-predominant soleus muscle was collected. We examined fiber composition, fiber cross-sectional area, capillary density, and fibrosis. Molecular analyses were also performed. To investigate the clinical relevance of this model, the oxidative-predominant, vastus lateralis muscle from patients with HFpEF was biopsied and examined for molecular changes in mitochondrial oxidative phosphorylation, vasculature, fibrosis, and inflammation. Histological analyses demonstrated a reduction in the abundance of oxidative fibers, type-2A fiber atrophy, decreased capillary density, and increased fibrotic area in the soleus muscle of HFpEF mice compared to Sham. Expression of targets of interest such as a reduction in mitochondrial oxidative-phosphorylation genes, increased VEGF-α and an elevated inflammatory response was also seen. The histological and molecular changes in HFpEF mice are consistent and comparable with changes seen in the oxidative-predominant SkM of patients with HFpEF. The HFpEF SAUNA model recapitulates the SkM phenotypic switching seen in HFpEF patients. This model is suitable and relevant to study SkM phenotypic switching in HFpEF.
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影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
3.3
作者：
Haddad, F;Zaldivar, F;Adams, GR
通讯作者：
Adams, GR
影响因子：
24.3
作者：
Abdellaoui, A.;Prefaut, C.;Hayot, M.
通讯作者：
Hayot, M.
DOI：
10.1016/j.omtm.2021.03.013
发表时间：
2021-06-11
期刊：
Molecular therapy. Methods & clinical development
影响因子：
--
作者：
Bosco J;Zhou Z;Gabriëls S;Verma M;Liu N;Miller BK;Gu S;Lundberg DM;Huang Y;Brown E;Josiah S;Meiyappan M;Traylor MJ;Chen N;Asakura A;De Jonge N;Blanchetot C;de Haard H;Duffy HS;Keefe D
通讯作者：
Keefe D
影响因子：
5.5
作者：
Birbrair, Alexander;Zhang, Tan;Delbono, Osvaldo
通讯作者：
Delbono, Osvaldo