人类HFpEF的严重肥胖会改变收缩蛋白的功能和组织，这一成果由约翰斯·霍普金斯大学
研究人员发现，与肥胖程度较低的HFpEF和非衰竭对照（NF）±肥胖相比，严重肥胖和HFpEF患者的心肌细胞收缩储备非常低，包括钙和长度刺激的张力、能量和肌球蛋白激活降低，但与EF降低的晚期HF相似。心肌细胞缺陷与HFpEF患者的体重指数和运动血流动力学相关，但与NF无关，并且在体重减轻后似乎是可逆的Thr181处的肌钙蛋白-I磷酸化升高仅发生在HF+肥胖导致的肌节功能障碍中。减肥和肌节增强剂可能对肥胖的HFpEF有好处。
据悉，保留射血分数（HFpEF）的心力衰竭具有很高的发病率和死亡率，并且几乎没有有效的治疗方法。随着时间的推移，其表型发生了变化，病态肥胖和代谢缺陷取代了高血压和心脏肥大。
附：英文原文
Title: Severe obesity in human HFpEF alters contractile protein function and organization
Author: Vivek P. Jani, Marcus Rhodehamel, Axel J. Fenwick, Weikang Ma, Eli Fisher, Maria T. Giannakopoulos, Sun Moon, Romi L. Castillo, Leslie M. Kennedy, Thomas C. Irving, Jil C. Tardiff, Elizabeth Murphy, Raghothama Chaerkady, Qing Wang, Meaghan E. Barry, Virginia S. Hahn, Kavita Sharma, Kenneth B. Margulies, Kenneth C. BediJr, Anthony Cammarato, David A. Kass
Issue&Volume: 2026-04-23
Abstract: Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality and has few effective therapies. Its phenotype has changed over time, with morbid obesity and metabolic defects supplanting hypertension and cardiac hypertrophy. We reveal that cardiomyocytes from patients with severe obesity and HFpEF have very depressed contractile reserve, including reduced calcium- and length-stimulated tension, power, and myosin activation compared to less-obese HFpEF and non-failing (NF) controls ±obesity, but similar to advanced HF with reduced EF. Myocyte defects correlate with body mass index and exercise hemodynamics in patients with HFpEF but not NF and appear reversible upon weight loss. Increased troponin-I phosphorylation at Thr181 occurs only in HF+obesity contributing to sarcomere dysfunction. Weight reduction and sarcomere enhancers may offer benefits in HFpEF with obesity.
DOI: adz7118
Source: https://www.science.org/doi/10.1126/science.adz7118