Cellular and molecular pathobiology of heart failure with preserved ejection fraction.
Cellular and molecular pathobiology of heart failure with preserved ejection fraction.
复制标题
射血分数保留的心力衰竭的细胞与分子病理生物学
DOI：
10.1038/s41569-020-00480-6
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Kass DA
中科院分区：
文献类型：
--
作者：
Mishra S;Kass DA
射血分数保留型心力衰竭（HFpEF）影响着全球半数心力衰竭患者，其患病率不断上升，发病率和死亡率颇高，且几乎没有被证明有效的治疗方法。可以说，它代表了心血管疾病中最大的未被满足的医疗需求，在整个医学领域都非常突出。虽然最初它是一种以高血压、心肌肥厚和舒张功能障碍为特征的疾病，但该综合征受到肥胖和糖尿病流行的极大影响，目前被认为是一种涉及心脏、肺、肾、骨骼肌、脂肪组织、免疫/炎症信号传导和血管系统的多系统疾病。这使得在实验动物中模拟该疾病变得困难，因为它不仅仅是哺乳动物中伴有异常舒张的心肌肥厚和高血压。然而，涉及血流动力学和代谢性疾病的新模型以及对人类病理生理学研究的不断努力，正在揭示新的信号传导和潜在的治疗靶点。本综述广泛探讨了HFpEF的基本病理生物学，尽管主要关注与心脏相关的机制，因为现有的大多数研究都集中在这个器官上。也就是说，也对包括骨骼肌、肺和肾在内的外周器官系统以及全身性生物标志物进行了研究，并介绍了正在进行的治疗工作。目的是提供一份正在揭示的信号传导和机制的路线图，最终可能会产生更具针对性、对临床有影响的治疗方法。
Heart failure with a preserved ejection fraction (HFpEF) affects half of all patients with HF worldwide, has an increasing prevalence, substantial morbidity and mortality, and very few treatments have proven to be effective. It arguably represents the greatest unmet medical need in cardiovascular disease and is certainly very prominent across all medicine. While initially a disorder characterized by hypertension, hypertrophy and diastolic dysfunction, the syndrome has become greatly impacted by the pandemic of obesity and diabetes and is currently recognized as a multisystem disorder involving heart, pulmonary, renal, skeletal muscle, adipose tissue, immune/inflammatory signalling and vascular systems. This has made it hard to mimic in experimental animals, as it is not simply hypertrophy and hypertension with abnormal relaxation in a mammal. However, new models involving both hemodynamic and metabolic disease, and increasing efforts to examine human pathophysiology, are revealing new signalling and potential therapeutic targets. This Review tackles the basic pathobiology of HFpEF broadly, though a major focus is on mechanisms pertinent to the heart as most of the existing research has focused on this organ. That said, there is also examination of peripheral organ systems, including skeletal muscle, lung, and kidney, as well as systemic biomarkers, and ongoing therapeutic efforts. The goal is to provide a mechanistic road-map of signalling and mechanisms that are being revealed and may finally lead to more patient-specific therapies with clinical impact.
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作者：
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发表时间：
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