Habecker Beth A, Bers Donald M, Birren Susan J, Chang Rui, Herring Neil, Kay Matthew W, Li Dan, Mendelowitz David, Mongillo Marco, Montgomery Johanna M, Ripplinger Crystal M, Tampakakis Emmanouil, Winbo Annika, Zaglia Tania, Zeltner Nadja, Paterson David J
Department of Chemical Physiology & Biochemistry, Department of Medicine Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
Department of Pharmacology, University of California, Davis School of Medicine, Davis, CA, USA.
J Physiol. 2025 Mar;603(7):1689-1728. doi: 10.1113/JP284739. Epub 2024 May 22.
This paper updates and builds on a previous White Paper in this journal that some of us contributed to concerning the molecular and cellular basis of cardiac neurobiology of heart disease. Here we focus on recent findings that underpin cardiac autonomic development, novel intracellular pathways and neuroplasticity. Throughout we highlight unanswered questions and areas of controversy. Whilst some neurochemical pathways are already demonstrating prognostic viability in patients with heart failure, we also discuss the opportunity to better understand sympathetic impairment by using patient specific stem cells that provides pathophysiological contextualization to study 'disease in a dish'. Novel imaging techniques and spatial transcriptomics are also facilitating a road map for target discovery of molecular pathways that may form a therapeutic opportunity to treat cardiac dysautonomia.
本文是对本期刊之前一篇白皮书的更新与拓展，我们中的一些人曾参与撰写那篇关于心脏病心脏神经生物学的分子和细胞基础的白皮书。在此，我们重点关注支撑心脏自主神经发育、新型细胞内信号通路和神经可塑性的最新研究发现。贯穿全文，我们突出了尚未解答的问题和存在争议的领域。虽然一些神经化学通路已在心力衰竭患者中显示出预后可行性，但我们也讨论了利用患者特异性干细胞更好地理解交感神经损伤的机会，这种干细胞能为在“培养皿中研究疾病”提供病理生理背景。新型成像技术和空间转录组学也为发现可能构成治疗心脏自主神经功能异常治疗机会的分子通路的靶点绘制了路线图。
