ArticleJCI insight2021
α7 Nicotinic acetylcholine receptor mediates right ventricular fibrosis and diastolic dysfunction in pulmonary hypertension.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- α7-nAChR Activation is Associated with Attenuation of Cardiac Fibrosis in Ischemic Cardiomyopathy via SIRT3-Dependent Modulation of EndMT.Journal of cardiovascular translational research · 2026Article
- Mitochondrial CaCommunications biology · 2026Article
- Activation of α7nAChR prevents maladaptive right ventricular remodeling via inhibiting the recruitment of CCR2Respiratory research · 2026Article
- Alpha-7 nicotinic acetylcholine receptor: targeting the interplay between inflammation, renin-angiotensin aldosterone system, and nervous system for the novel treatment of heart failure.Frontiers in pharmacology · 2026Review
- Modulatory roles of the vagus nerve and nicotine in bleomycin-induced pulmonary fibrosis in rats.BMC pulmonary medicine · 2025Article
- Right Ventricular Fibrosis With Pulmonary Arterial Hypertension.Reviews in cardiovascular medicine · 2025Review
- Negative Air Ions Attenuate Nicotine-Induced Vascular Endothelial Dysfunction by Suppressing AP1-Mediated FN1 and SPP1.Antioxidants (Basel, Switzerland) · 2025Article
- Dissecting contributions of pulmonary arterial remodeling to right ventricular afterload in pulmonary hypertension.Bioengineering & translational medicine · 2025Article
- Article
- Right Ventricular Stiffening and Anisotropy Alterations in Pulmonary Hypertension: Mechanisms and Relations to Right Heart Failure.Journal of the American Heart Association · 2025Article
- Cholinesterase inhibitors and reduced risk of hospitalization and mortality in patients with Alzheimer's dementia and heart failure.European heart journal. Cardiovascular pharmacotherapy · 2025Article
- Vagal Splenic-Dependent Effects Influence Glucose Homeostasis, Insulin Secretion, and Histopathology of the Endocrine Pancreas in Hypothalamic Obese Male Rats: Vagus Nerve and Spleen Interactions Affect the Endocrine Pancreas.TheScientificWorldJournal · 2025Article
- Echocardiographic assessment and new advances of right ventricle function in rats with pulmonary hypertension.Frontiers in pharmacology · 2025Review
- Pathophysiology of the right ventricle and its pulmonary vascular interaction.The European respiratory journal · 2024Review
- [Research progress of right ventricular strain imaging evaluation technology in pulmonary arterial hypertension].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Review
- Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?"Cardiovascular toxicology · 2024Review
- Translational implications of CHRFAM7A, an elusive human-restricted fusion gene.Molecular psychiatry · 2024Review
- Reduced exercise capacity occurs before intrinsic skeletal muscle dysfunction in experimental rat models of pulmonary hypertension.Pulmonary circulation · 2024Article
- Adeno-associated virus-based approach for genetic modification of cardiac fibroblasts in adult rat hearts.Physiological reports · 2024Article
- Circulating acetylcholine serves as a potential biomarker role in pulmonary hypertension.BMC pulmonary medicine · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Right ventricular (RV) fibrosis is a key feature of maladaptive RV hypertrophy and dysfunction and is associated with poor outcomes in pulmonary hypertension (PH). However, mechanisms and therapeutic strategies to mitigate RV fibrosis remain unrealized. Previously, we identified that cardiac fibroblast α7 nicotinic acetylcholine receptor (α7 nAChR) drives smoking-induced RV fibrosis. Here, we sought to define the role of α7 nAChR in RV dysfunction and fibrosis in the settings of RV pressure overload as seen in PH. We show that RV tissue from PH patients has increased collagen content and ACh expression. Using an experimental rat model of PH, we demonstrate that RV fibrosis and dysfunction are associated with increases in ACh and α7 nAChR expression in the RV but not in the left ventricle (LV). In vitro studies show that α7 nAChR activation leads to an increase in adult ventricular fibroblast proliferation and collagen content mediated by a Ca2+/epidermal growth factor receptor (EGFR) signaling mechanism. Pharmacological antagonism of nAChR decreases RV collagen content and improves RV function in the PH model. Furthermore, mice lacking α7 nAChR exhibit improved RV diastolic function and have lower RV collagen content in response to persistently increased RV afterload, compared with WT controls. These finding indicate that enhanced α7 nAChR signaling is an important mechanism underlying RV fibrosis and dysfunction, and targeted inhibition of α7 nAChR is a potentially novel therapeutic strategy in the setting of increased RV afterload.
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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.