Department of Internal Medicine and Cardiology, Technische Universität Dresden, Heart Center Dresden - University Hospital, Herzzentrum Dresden, Universitätsklinik, Fetscherstraße 76, Dresden, 01307, Germany.
Dresden Cardiovascular Research Institute and Core Laboratories GmbH, Dresden, Germany.
ESC Heart Fail. 2021 Aug;8(4):2556-2568. doi: 10.1002/ehf2.13405. Epub 2021 May 5.
Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin-proteasome-system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing.
Patients with HFpEF (LVEF ≥ 50%, septal E/e' > 15 or >8 and NT-proBNP > 220 pg/mL, n = 20), HFrEF (LVEF ≤ 35%, n = 20) and sedentary control subjects (Con, n = 12) were studied. Inflammatory markers were measured in serum, and markers of the UPS, nuclear apoptosis, and energy metabolism were determined in percutaneous SM biopsies. Both HFpEF and HFrEF showed increased proteolysis (MuRF-1 protein expression, ubiquitination, and proteasome activity) with proteasome activity significantly related to interleukin-6. Proteolysis was more pronounced in patients with lower exercise capacity as indicated by peak oxygen uptake in per cent predicted below the median. Markers of apoptosis did not differ between groups. Mitochondrial energy supply was reduced in HFpEF and HFrEF (complex-I activity: -31% and -53%; malate dehydrogenase activity: -20% and -29%; both P < 0.05 vs. Con). In contrast, short-term energy supply via creatine kinase was increased in HFpEF but decreased in HFrEF (47% and -45%; P < 0.05 vs. Con).
Similarly to HFrEF, skeletal muscle in HFpEF is characterized by increased proteolysis linked to systemic inflammation and reduced exercise capacity. Energy metabolism is disturbed in both groups; however, its regulation seems to be severity-dependent.
骨骼肌（SM）改变导致射血分数保留（HFpEF）或降低（HFrEF）的心力衰竭患者运动不耐受。通过泛素-蛋白酶体系统（UPS）、核凋亡和减少的线粒体能量供应导致 HFrEF 中的 SM 减弱，与这种 SM 减弱相关。这些机制在 HFpEF 中研究不充分，并且这些组之间缺乏直接比较。
研究了 HFpEF 患者（LVEF≥50%，间隔 E/e' > 15 或 >8 和 NT-proBNP > 220 pg/mL，n=20）、HFrEF 患者（LVEF≤35%，n=20）和久坐对照组（Con，n=12）。测量了血清中的炎症标志物，并在经皮 SM 活检中测定了 UPS、核凋亡和能量代谢的标志物。HFpEF 和 HFrEF 均显示出蛋白水解增加（MuRF-1 蛋白表达、泛素化和蛋白酶体活性），蛋白酶体活性与白细胞介素-6 显著相关。在根据中位数以下的峰值摄氧量将运动能力分为低和高的患者中，蛋白酶解作用更为明显。两组之间凋亡标志物无差异。HFpEF 和 HFrEF 中的线粒体能量供应减少（复合物-I 活性：-31%和-53%；苹果酸脱氢酶活性：-20%和-29%；均 P<0.05 与 Con 相比）。相比之下，HFpEF 中的短期能量供应通过肌酸激酶增加，但在 HFrEF 中减少（47%和-45%；P<0.05 与 Con 相比）。
与 HFrEF 相似，HFpEF 中的骨骼肌以与全身炎症和运动能力降低相关的蛋白水解增加为特征。两组的能量代谢均受到干扰；然而，其调节似乎取决于严重程度。
