ArticleCirculation2021
Fibroblast-Specific Proteotranscriptomes Reveal Distinct Fibrotic Signatures of Human Sinoatrial Node in Nonfailing and Failing Hearts.
Article in Circulation, 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, 48 citations in OpenAlex.
- Periostin-CCL3 Feedforward Signaling Loop Promotes Cardiac Fibrosis and Cardiomyocyte Necroptosis in Arrhythmogenic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A novel multicellular model of the adult mouse sinoatrial node retains spontaneous electrical activity and enables live investigation of the S100B-associated cell population.bioRxiv : the preprint server for biology · 2026Article
- Characterization of p16-positive stromal cells in age-related cardiac disorders.Journal of biochemistry · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Emerging Regulatory Mechanisms in Sinoatrial Node Automaticity.Journal of cellular and molecular medicine · 2026Review
- Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models.Nature communications · 2025Article
- Microvascular Rarefaction in the Sinoatrial Node: A Potential Mechanism for Pacemaker Dysfunction in Early HFpEF.JACC. Clinical electrophysiology · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription.Cell death & disease · 2025Article
- Heart Rate Mystery Unveiled: Sex Differences in Human Sinoatrial Node Genes and Female Tachycardia.Circulation. Arrhythmia and electrophysiology · 2025Article
- Tissue elasticity modulates cardiac pacemaker cell automaticity.American journal of physiology. Heart and circulatory physiology · 2025Article
- Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure.Circulation research · 2025Review
- Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction.Cardiovascular research · 2024Article
- Risk factors for postoperative delirium in frail elderly patients undergoing on-pump cardiac surgery and development of a prediction model-a prospective observational study.Frontiers in cardiovascular medicine · 2024Article
- Sinoatrial node heterogeneity and fibroblasts increase atrial driving capability in a two-dimensional human computational model.Frontiers in physiology · 2024Article
- Mechanistic insight into the functional role of human sinoatrial node conduction pathways and pacemaker compartments heterogeneity: A computer model analysis.PLoS computational biology · 2023Article
- Transcriptomic profile of the mechanosensitive ion channelome in human cardiac fibroblasts.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis.Cellular & molecular biology letters · 2023Article
- What makes the sinoatrial node tick? A question not for the faint of heart.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Local tissue mechanics control cardiac pacemaker cell embryonic patterning.Life science alliance · 2023Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundUp to 50% of the adult human sinoatrial node (SAN) is composed of dense connective tissue. Cardiac diseases including heart failure (HF) may increase fibrosis within the SAN pacemaker complex, leading to impaired automaticity and conduction of electric activity to the atria. Unlike the role of cardiac fibroblasts in pathologic fibrotic remodeling and tissue repair, nothing is known about fibroblasts that maintain the inherently fibrotic SAN environment.
methodsIntact SAN pacemaker complex was dissected from cardioplegically arrested explanted nonfailing hearts (non-HF; n=22; 48.7±3.1 years of age) and human failing hearts (n=16; 54.9±2.6 years of age). Connective tissue content was quantified from Masson trichrome-stained head-center and center-tail SAN sections. Expression of extracellular matrix proteins, including collagens 1 and 3A1, CILP1 (cartilage intermediate layer protein 1), and POSTN (periostin), and fibroblast and myofibroblast numbers were quantified by in situ and in vitro immunolabeling. Fibroblasts from the central intramural SAN pacemaker compartment (≈10×5×2 mm
resultsIntranodal fibrotic content was significantly higher in SAN pacemaker complex from HF versus non-HF hearts (57.7±2.6% versus 44.0±1.2%;
conclusionsThis study revealed increased SAN-specific fibrosis with presence of myofibroblasts, CILP1, and POSTN-positive interstitial fibrosis only in HF versus non-HF human hearts. Comprehensive proteotranscriptomic profiles of SAN fibroblasts identified upregulation of genes and proteins promoting stiffer SAN extracellular matrix in HF hearts. Fibroblast-specific profiles generated by our proteotranscriptomic analyses of the human SAN provide a comprehensive framework for future studies to investigate the role of SAN-specific fibrosis in cardiac rhythm regulation and arrhythmias.
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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 Socratic graph.