Vahle Beatrice, Klädtke Romy, Schauer Antje, Bowen T Scott, Wisløff Ulrik, Linke Axel, Adams Volker
Laboratory of Molecular and Experimental Cardiology, University Clinic, Department of Internal Medicine, Heart Center, University of Technology Dresden, 01307 Dresden, Germany.
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Int J Mol Sci. 2025 Jun 27;26(13):6196. doi: 10.3390/ijms26136196.
Heart failure with preserved ejection fraction (HFpEF) shows diverse disease patterns, with various combinations of comorbidities and symptoms. A common hallmark is exercise intolerance, caused by alterations in the peripheral skeletal muscle (SKM) including a recently indicated titin hyperphosphorylation. Our aim is to compare a metabolic syndrome- (ZSF-1 rats) and a hypertension-driven (Dahl salt-sensitive (DSS) rats) HFpEF rat-model in relation to SKM function and titin phosphorylation. Obese ZSF-1 and high-salt fed DSS rats (HFpEF) were compared to lean ZSF-1 and low-salt fed rats (con). HFpEF was confirmed by echocardiography and invasive haemodynamic measurements. SKM atrophy, in vitro force measurements, titin- and contractile protein expression were evaluated. Obese ZSF-1 HFpEF rats showed muscle atrophy, reduced muscle force and increased titin phosphorylation compared to controls, which was not detected in hypertensive DSS rats. Fiber type specific troponins, myostatin and four and a half LIM domain 1 were differently regulated between the two models. Altogether, our results show that both animal models of HFpEF exhibit different SKM phenotypes, probably based on the divergent disease etiologies, which may help to define the most suitable animal model for HFpEF to test potential treatment regimens.
射血分数保留的心力衰竭（HFpEF）表现出多样的疾病模式，伴有多种合并症和症状组合。一个共同特征是运动不耐受，这是由外周骨骼肌（SKM）的改变引起的，包括最近发现的肌联蛋白过度磷酸化。我们的目的是比较代谢综合征驱动的（ZSF-1大鼠）和高血压驱动的（Dahl盐敏感（DSS）大鼠）HFpEF大鼠模型在SKM功能和肌联蛋白磷酸化方面的差异。将肥胖的ZSF-1大鼠和高盐喂养的DSS大鼠（HFpEF）与瘦的ZSF-1大鼠和低盐喂养的大鼠（对照）进行比较。通过超声心动图和有创血流动力学测量来确认HFpEF。评估SKM萎缩、体外肌力测量、肌联蛋白和收缩蛋白表达。与对照组相比，肥胖的ZSF-1 HFpEF大鼠表现出肌肉萎缩、肌力降低和肌联蛋白磷酸化增加，而在高血压DSS大鼠中未检测到这些情况。两种模型之间纤维类型特异性肌钙蛋白、肌肉生长抑制素和四半LIM结构域1的调节方式不同。总之，我们的结果表明，两种HFpEF动物模型表现出不同的SKM表型，这可能基于不同的疾病病因，这可能有助于确定最适合用于测试潜在治疗方案的HFpEF动物模型。
