Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Advanced Clinical Biosystems Research Institute, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Nat Cardiovasc Res. 2024 Aug;3(8):907-914. doi: 10.1038/s44161-024-00516-x. Epub 2024 Jul 25.
Over half of patients with heart failure have a preserved ejection fraction (>50%, called HFpEF), a syndrome with substantial morbidity/mortality and few effective therapies. Its dominant comorbidity is now obesity, which worsens disease and prognosis. Myocardial data from patients with morbid obesity and HFpEF show depressed myocyte calcium-stimulated tension and disrupted gene expression of mitochondrial and lipid metabolic pathways, abnormalities shared by human HF with a reduced EF but less so in HFpEF without severe obesity. The impact of severe obesity on human HFpEF myocardial ultrastructure remains unexplored. Here we assessed the myocardial ultrastructure in septal biopsies from patients with HFpEF using transmission electron microscopy. We observed sarcomere disruption and sarcolysis, mitochondrial swelling with cristae separation and dissolution and lipid droplet accumulation that was more prominent in the most obese patients with HFpEF and not dependent on comorbid diabetes. Myocardial proteomics revealed associated reduction in fatty acid uptake, processing and oxidation and mitochondrial respiration proteins, particularly in very obese patients with HFpEF.
超过一半的心衰患者射血分数保留（>50%，称为 HFpEF），这是一种发病率/死亡率高但治疗方法有限的综合征。其主要合并症是肥胖，它会使病情和预后恶化。肥胖症和 HFpEF 患者的心肌数据显示，钙离子刺激张力降低和线粒体和脂质代谢途径的基因表达紊乱，这些异常在 EF 降低的人类心衰中共同存在，但在没有严重肥胖的 HFpEF 中则不那么明显。严重肥胖对人类 HFpEF 心肌超微结构的影响仍不清楚。在这里，我们使用透射电子显微镜评估了 HFpEF 患者间隔活检的心肌超微结构。我们观察到肌节破坏和肌溶解，线粒体肿胀伴嵴分离和溶解以及脂滴积累，这种情况在肥胖程度最严重的 HFpEF 患者中更为明显，而且与合并糖尿病无关。心肌蛋白质组学显示与脂肪酸摄取、加工和氧化以及线粒体呼吸蛋白相关的减少，尤其是在肥胖程度非常严重的 HFpEF 患者中。
