Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: We previously showed in a rat model of heart failure with preserved ejection fraction (HFpEF) that transcutaneous vagus nerve stimulation (tVNS) reduced cardiac fibrosis and inflammation. However, macrophage-mediated mechanisms through which tVNS rescues cardiac function remain poorly understood.
Methods: We induced HFpEF in 8-week-old mice by a combination of a high-fat diet and l-NG-nitro arginine methyl ester for 5 weeks, followed by 4 weeks of tVNS or sham stimulation. At this time, we analyzed cardiac function by echocardiography and immune cell numbers by single-cell RNA sequencing and flow cytometry.
Results: Our data demonstrate that HFpEF mice exhibited diastolic dysfunction, left ventricular hypertrophy, and fibrosis, consistent with HFpEF, and that tVNS significantly improved HFpEF severity. Analysis of merged single-cell RNA sequencing data from control, HFpEF+sham, and HFpEF+tVNS mice showed that HFpEF was associated with the accumulation of -expressing CCR2 (C-C chemokine receptor type 2) cardiac resident macrophages (CRM). Furthermore, treatment with tVNS reduced the number of CCR2 CRM and the expression of while also inducing the expression of in TLF (Timd4 [T-cell immunoglobulin and mucin domain containing 4]/Lyve1 [Lymphatic vessel endothelial hyaluronan receptor 1]/Folr2 [Folate receptor 2]) and MHC2(Major histocompatibility complex 2) CRM. Global deletion of or blockade of CCR2 CRM recruitment improved HFpEF, whereas TLF/MHC2 specific deletion of reversed the protective effect of tVNS on HFpEF. The benefits of tVNS were also abolished in the setting of disrupted acetylcholine/α7nAChR (α7 nicotinic acetylcholine receptor) signaling, either via pharmacological inhibition of α7nAChR or choline acetyltransferase deletion in CD4 (cluster of differentiation) T cells.
Conclusions: Collectively, our data indicate that tVNS improves HFpEF by reducing expressing CCR2 CRM and inducing expression of proreparative in TLF/MHC2 CRM. These effects are mediated through cholinergic signaling, highlighting a neuroimmune pathway in HFpEF.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266641 | PMC |
| http://dx.doi.org/10.1161/CIRCRESAHA.125.326236 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Vagal Stimulation Rescues HFpEF by Altering Cardiac Resident Macrophage Function.
Circ Res
August 2025
Cardiovascular Section, Department of Medicine (T.V., M.T., M.N., K.F., L.M., K.E., S.W., S.S.), University of Oklahoma Health Science Center.
Background: We previously showed in a rat model of heart failure with preserved ejection fraction (HFpEF) that transcutaneous vagus nerve stimulation (tVNS) reduced cardiac fibrosis and inflammation. However, macrophage-mediated mechanisms through which tVNS rescues cardiac function remain poorly understood.
Methods: We induced HFpEF in 8-week-old mice by a combination of a high-fat diet and l-NG-nitro arginine methyl ester for 5 weeks, followed by 4 weeks of tVNS or sham stimulation.
A functional cardiac patch promotes cardiac repair by modulating the CCR2 cardiac-resident macrophage niche and their cell crosstalk.
Cell Rep Med
February 2025
Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China; Guangd
C-C chemokine receptor type 2 (CCR2) cardiac-resident macrophages (CCR2 cRMs) are known to promote cardiac repair after myocardial infarction (MI). However, the substantial depletion and slow recovery of CCR2 cRMs pose significant barriers in cardiac recovery. Here, we construct a functional conductive cardiac patch (CCP) that can provide exogenously elastic conductive microenvironment and induce endogenously reparative microenvironment mediated by CCR2 cRMs for MI repair.
View Article and Find Full Text PDFTranscriptomic profiling and regulatory pathways of cardiac resident macrophages in aging.
Cell Mol Life Sci
May 2024
Department of Cardiology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai, China.
Cardiovascular diseases are an array of age-related disorders, and accumulating evidence suggests a link between cardiac resident macrophages (CRMs) and the age-related disorders. However, how does CRMs alter with aging remains elusive. In the present study, aged mice (20 months old) have been employed to check for their cardiac structural and functional alterations, and the changes in the proportion of CRM subsets as well, followed by sorting of CRMs, including C-C Motif Chemokine Receptor 2 (CCR2) and CCR2 CRMs, which were subjected to Smart-Seq.
View Article and Find Full Text PDFRenewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation Jagged-1-Notch1.
Acta Pharm Sin B
January 2023
International Genome Center, Jiangsu University, Zhenjiang 212013, China.
Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration.
View Article and Find Full Text PDFEnvironmental Enrichment Rescues Functional Deficit and Alters Neuroinflammation in a Transgenic Model of Tauopathy.
J Alzheimers Dis
April 2021
Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovakia.
Article Synopsis
- Alzheimer's disease (AD) is a leading neurodegenerative disorder affecting over 44 million people, and there are currently no effective drugs for its prevention or treatment.
- A study involving transgenic rat models showed that exposure to an enriched environment for 3 months improved behavioral deficits without reducing tau pathology, indicating that environmental factors can positively influence functioning in AD models.
- The research also found increased nerve growth factor levels in the hippocampus of both transgenic and non-transgenic rats, while inflammation markers were altered, suggesting non-pharmacological approaches might help mitigate neuroinflammation related to tau protein in AD.