ArticleThe Journal of clinical investigation2010
Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Cardiac sympathetic hyperinnervation after myocardial infarction: a systematic review and qualitative analysis.Annals of medicine · 2023Pooled it
- Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM-HFpEF study.ESC heart failure · 2018Trial
- Pancreatic cancer cachexia promotes cardiac dysfunction through altered adrenergic signalling in the heart.The Journal of physiology · 2026Article
- Satellite Glial Cells Drive Homeostatic Synaptic Structural Plasticity in Sympathetic Neurons.bioRxiv : the preprint server for biology · 2026Article
- Molecular and functional diversity of the autonomic nervous system.Nature reviews. Neuroscience · 2025Review
- Neurocardiology: translational advancements and potential.The Journal of physiology · 2025Review
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Cardiac Sympathetic Innervation and Ventricular Arrhythmias in Structural Heart Disease: Current Peripheral Neuromodulation Therapies and Emerging Therapeutic Targets.Arrhythmia & electrophysiology review · 2025Review
- Hypertension-induced heart failure disrupts cardiac sympathetic innervation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Blockade of mesenteric and omental adipose tissue sensory neurons improves cardiac remodeling through sympathetic pathway.iScience · 2024Article
- Sympathetic Neural Control at Rest and During the Cold Pressor Test in Patients With Heart Failure With Preserved Ejection Fraction.Hypertension (Dallas, Tex. : 1979) · 2024Article
- The Intrinsic Cardiac Nervous System: From Pathophysiology to Therapeutic Implications.Biology · 2024Review
- Circulating acetylcholine serves as a potential biomarker role in pulmonary hypertension.BMC pulmonary medicine · 2024Article
- Neurochemical alterations of intrinsic cardiac ganglionated nerve plexus caused by arterial hypertension developed during ageing in spontaneously hypertensive and Wistar Kyoto rats.Journal of anatomy · 2023Article
- Vagal Nerve Stimulation Reduces Ventricular Arrhythmias and Mitigates Adverse Neural Cardiac Remodeling Post-Myocardial Infarction.JACC. Basic to translational science · 2023Article
- Autonomic control of ventricular function in health and disease: current state of the art.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023Review
- Sympathetic Modulation in Cardiac Arrhythmias: Where We Stand and Where We Go.Journal of personalized medicine · 2023Review
- Cholinergic collaterals arising from noradrenergic sympathetic neurons in mice.The Journal of physiology · 2023Article
- Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer's disease.Frontiers in physiology · 2023Review
- The susceptibility of cardiac arrhythmias after spinal cord crush injury in rats.Experimental neurology · 2022Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.