Clinical neurocardiology: defining the value of neuroscience‐based cardiovascular therapeutics – 2024 update

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

The intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function ANS is central to pathophysiology cardiovascular diseases. It stands reason, therefore, that neuroscience-based therapeutics hold great promise treatment diseases humans. A decade after inaugural edition, this White Paper reviews current state understanding human neuroanatomy, neurophysiology and specific disease conditions, testing, risk stratification, neuromodulatory strategies mitigate progression

Language: Английский

---

Cardiac sympathetic neurons are additional cells affected in genetically determined arrhythmogenic cardiomyopathy

The Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 14, 2024

Arrhythmogenic cardiomyopathy (AC) is a familial cardiac disease, mainly caused by mutations in desmosomal genes, which accounts for most cases of stress-related arrhythmic sudden death, young and athletes. AC hearts display fibro-fatty lesions that generate the substrate cause contractile dysfunction. A correlation between physical/emotional stresses arrhythmias supports involvement sympathetic neurons (SNs) but this has not been confirmed previously. Here, we combined molecular, vitro ex vivo analyses to determine role AC-linked DSG2 downregulation on SN biology assess innervation desmoglein-2 mutant (Dsg2

Language: Английский

---

The emerging roles of cardiac sympathetic innervation in arrhythmogenic cardiomyopathy

International Journal of Cardiology, Journal Year: 2025, Volume and Issue: unknown, P. 133006 - 133006

Published: Jan. 1, 2025

Language: Английский

---

Catecholaminergic Polymorphic Ventricular Tachycardia: Advancing From Molecular Insights to Preclinical Models

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Inherited cardiac channelopathies are linked to a heightened risk of sudden death. Despite evolving knowledge on different genes for these inherited conditions, certain subtypes, such as catecholaminergic polymorphic ventricular tachycardia syndrome, the specific genetic causes remain unidentified. The research pathophysiological mechanisms underlying syndrome has been conducted through in vitro and vivo models, including genetically modified animal cardiac‐specific transgenic pharmacological interventions human‐induced pluripotent stem cell–derived cardiomyocytes 2‐ 3‐dimensional models. Recent predominantly utilizes cardiomyocytes, focusing genotype–phenotype correlations screening. integration cutting‐edge techniques clustered regularly interspaced short palindromic repeats/Cas9 genome editing 3‐dimensional–engineered heart tissues shed new light tachycardia, potentially enhancing drug therapies part personalized medicine approaches. This review emphasizes diverse insights gained from both studies along with application models various contexts.

Language: Английский

---

Preface Editorial for Special Issue Dedicated to Jeffrey L. Ardell (1952–2025) Cardiac Neurobiology: Concepts to Clinic

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

In 2016, we published a special issue concerned with cardiac autonomic control in health and disease (Shivkumar & Ardell, 2016). Since then, there has been an explosion of scientific interest the neurobiology nervous system (Herring et al., 2019; Paton unpublished raw data) aimed at understanding how neuromodulation can be used therapeutically to treat (La Rovere 2020; Hanna, Buch 2021; Hadaya 2020). To bridge areas neurology cardiology, emerging field neurocardiology bioelectronic medicine or 'neuroceutics' is now receiving significant attention funding as priority area from NIH (National Institutes Health, Office Strategic Coordination-The Common Fund. Stimulating Peripheral Activity Relieve Conditions – SPARC; University Minnesota awarded $21 million lead research revealing effects vagus nerve stimulation humans) Leducq Foundation (Paterson Shivkumar, 2023). The strategy underpinned by development personalised site-specific targeting end-organ function, particular arrhythmia. What becoming apparent importance bidirectional communication between neurons myocytes (Davis 2022) need have better complex neural architecture (Hanna, Dacey Rajendran 2019) that underpins rhythm disturbance 'little brain' heart (Armour 2008; Herring Paterson, 2021). Moreover, deeper appreciation circuits miniaturization sensor technology provided opportunity lay foundations for next generation bioelectronics closed loop (Lerman 2025). July 2024 Journal Physiology supported focused meeting Oxford was associated International Society Autonomic Neuroscience (ISAN 2024). This 2-day framework assemble opinion leaders also facilitated younger investigators bioengineering, physiological medical communities interact. this issue, entitled Cardiac Neurobiology: Concepts Clinic, highlight deliberations meeting. particular, starts update on three white papers which gather opinions 52 leading experts they review major advances taken place past 8 years. first paper Habecker al. (2025) addresses molecular cellular basis interactions disease. A focus novel intracellular pathways neuroplasticity explored, given spatial transcriptomics, interface patient-specific stem cells provides pathophysiological contextualization study 'disease dish'. use further highlighted in-depth topical Wu discusses current progress future prospects platform. utility approach illustrated Mohammadi who observed sympathetic induce more mature phenotype IPSC-derived myocytes, reinforcing notion cross-talk myocytes. Mapping these technologies translational advancements featured second 2025), explores our where target key sites (intracardiac system, stellate ganglia, nerve, dorsal root ganglia mid-brain nuclei brain are cardiovascular active). challenge here body's on-board 'homeostatic intelligence system' so closed-loop regulation therapies evolve. As Herring, Ardell colleagues discuss, will only achieved viable bioengineering develops respond appropriate biomarkers (both electrical mechanical) work endogenous systems optimize outcomes rather than opposition them. significance therapy pass dish pre-clinical environment. Importantly, transition demonstrate positive over above traditional pharmacological interventions if clinical reach achieved. point third extensive Ajijola (2025). Here, discuss challenges opportunities define value neuroscience-based therapeutics. They present updates trials involving hold promise prognostic indicators. Emerging evidence highlighting role neuropeptide Y (NPY) one biomarker post-myocardial infarction (MI) (Kalla co-released noradrenaline (NA) during states high drive, its Neil his Bayliss Starling Prize lecture (Bussmann 2023) article van Weperen elegantly showed circulating NA leads release NPY nerves via activation postganglionic pre-synaptic beta-adrenergic receptors. probably involved feedback cascade cause transmission both (Adler-Graschinsky Langer, 1975) because indeed adrenaline released diseased post-ganglionic bind beta-2 adrenergic receptors (Bardsley 2018). Vrabec (2025), modulation hyperexcitability through block shown mitigate pacing-induced heterogeneous catecholamine infarcted pig heart. highlights potential axonal titrate direct modulate neuronal excitability highly controllable fashion. relating structure function reviewed timely fashion Qu link ultrastructure different scales impulse conduction arrhythmogenesis. experimental data needed validate multiscale models provide increased predictability understand Ashton illustrates 3-D structural electrophysiological functional changes intracardiac linked atrial fibrillation (AF). Similarly, computational modelling control, following MI using silico patient cohort, employed Gee help explain heterogeneity vagal baroreflex after ischaemic injury. Interestingly, it reported individuals central peripheral efferent adaptation preserved baroreceptor gain could maintain sensitivity post-MI. Although promote AF, anti-arrhythmic ventricle behaves like nature's calcium channel blocker, why efforts properties selectively. Thompson undertook anatomical investigation looking organization fibres porcine cervical aim developing spatially selective neuromodulation. landmark Macefield laboratory (Farmer 2025) describes firing single axons rhythmicity human nerve. signatures patterns cycle patterning evolves Arrhythmogenic cardiomyopathy genetically determined disease, accounts most cases stress-related arrhythmic sudden death. Vanaja Zaglia Mongillo group identified additional affected mouse model arrhythmogenic mutations desmoglein-2. Altered innervation recognized characteristic may contribute aetiology itself. Indeed, remodelling feature many primary diseases such hypertension. Li blood pressure increases neuron activity enhancing intraganglionic cholinergic collateral connections ganglion. demonstrates occurs contributes dysautonomia. Ahmadian session acute intermittent hypoxia (IH) capable neuromodulating rat spinal cord injury disrupted bulbospinal pathway. Whether IH therapeutic similar remains determined, but earlier studies increase post ganglionic decreasing inhibitory action NO-cGMP pathway drive (Mohan 2001). Going forward, develop reproducibly recapitulate contextualization. end, IPSC organoid aid endeavour, especially strong genetic underpinning channelopathies. utilization other mammalian important show conservation structures transcripts proteins determine whether mimicked (Habecker 2025; data). Tompkins detailed described looked comparative specialization intrinsic (ICNs) humans, mice pigs. found conserved derived attributes within mammals enhance circuitry ICN conditions AF. Combined single-cell Gupta modelled heart's each genotype characterized unique combination ion channels mapped onto specific transcriptomic signature. 10 years, made bridging concept clinic. There still much do, results enhanced efficacy contemporary change practice. Closing gap cell-based technological bionanomaterials presents bring together community bioengineers, physiologists physicians. Our mission build precisely wiring save lives millions die every year arrest. editorial coauthored late Professor 2016) concluded, 'Neuromodulation based strategies meaningful tens going suddenly arrhythmias suffer serious morbidity ultimate death due failure coming years!' already started bear fruits issue. We state possibilities physiology very bright. dedicated Jeff close friend colleague, pioneer advocate neurocardiology. He sadly missed, legacy live pupils, he authored. Piam Memoriam. Please note: publisher not responsible content functionality any supporting information supplied authors. Any queries (other missing content) should directed corresponding author article. None declared. D.J.P K.S were conception design work; drafting revising critically intellectual content; approved final version submitted publication. Both authors agree accountable all aspects work. All persons designated qualify authorship, those authorship listed. D.J.P./K.S. Supported Network Excellence Award (23CVD04) Bioelectronics Neurocardiology.

Language: Английский

---

Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 28, 2025

The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs effective treatments systemic diseases. While animal models have traditionally been pivotal in studying interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing vitro models. Beyond conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids emerged a substantial advancement, capable of replicating essential structural functional attributes internal organs vitro. This breakthrough has spurred development multilineage organoids, assembloids, organoids-on-a-chip technologies, which allow enhanced physiological relevance. These technologies shown great potential mimicking coordinated organogenesis, exploring disease pathogenesis, facilitating drug discovery. As central system, heart serves focal point an extensively studied network interactions. review focuses on advancements challenges organs, presenting comprehensive exploration this cutting-edge approach research.

Language: Английский

---

Defining cardioception: Heart-brain crosstalk

Neuron, Journal Year: 2024, Volume and Issue: 112(22), P. 3671 - 3674

Published: Nov. 1, 2024

Language: Английский

---

The Reappraisal of Neuropeptide Y as Biomarker and Therapeutic Target in Arrhythmic Disorders

JACC. Clinical electrophysiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

---

How the brain impacts the heart: lessons from ischaemic stroke and other neurological disorders

Heart, Journal Year: 2024, Volume and Issue: unknown, P. heartjnl - 324173

Published: Nov. 7, 2024

Cardiovascular alterations are common in patients who had ischaemic stroke, haemorrhagic stroke and other acute brain disorders such as seizures. These cardiac complications important drivers of morbidity mortality comprise blood-based detection cardiomyocyte damage, ECG changes, heart failure arrhythmia. Recently, the concept a distinct 'stroke-heart syndrome' has been formulated pathophysiological framework for poststroke complications. The considers sequelae after to be result stroke-induced disturbance brain-heart axis. In this review, we describe spectrum changes secondary disorders. Furthermore, focus on Takotsubo syndrome model disease disturbed interaction. Finally, aim provide an overview anatomical functional links between heart, with emphasis autonomic network role inflammation. Given clinical relevance deleterious impact injury call awareness starting joint efforts combining expertise neurology cardiology identify specific therapeutic interventions.

Language: Английский

---