ArticleCell research2021
LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration.
Article in Cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Advances and Prospects in Using Induced Pluripotent Stem Cells for 3D Bioprinting in Cardiac Tissue Engineering.Reviews in cardiovascular medicine · 2025Pooled it
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Bench to Bedside: Insights from Large Animal Models and Emerging Clinical Trials of Endogenous Cardiac Regeneration and Repair.Journal of cardiovascular translational research · 2026Review
- Review
- Inhibiting L-type calcium channel promotes cardiomyocyte proliferation through activating the canonical Wnt signaling pathway.Acta pharmacologica Sinica · 2026Article
- PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF-β/Smad Signalling Pathway.Cell proliferation · 2026Article
- Restoration of RBM22 overcomes the transcriptional and epigenetic barriers of cardiomyocyte proliferation for heart regeneration.Nature communications · 2026Article
- OverlappING and DivergING roles of ING4 and ING5 in cancer, differentiation and development.Frontiers in cell and developmental biology · 2026Review
- Myocardial infarction creates a critical time window for AAV-based cardiac gene transfer.Fundamental research · 2025Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- ING5: multifaceted roles beyond tumor suppression in cellular physiology and disease.Epigenetics & chromatin · 2025Review
- Review
- Cardiomyocyte regeneration after infarction: changes, opportunities and challenges.Molecular and cellular biochemistry · 2025Review
- Intronic RNAscope probes enable precise identification of cardiomyocyte nuclei and cell cycle activity.Communications biology · 2025Article
- Jellyfish stings-induced cardiac failure was ameliorated through AAG-mediated glycogen-driven ATP production.Exploration (Beijing, China) · 2025Article
- Targeting Wnt Pathways with Small Molecules as New Approach in Cardiovascular Disease.Current cardiology reviews · 2025Review
- Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway.Frontiers in cardiovascular medicine · 2025Article
- Knockout of the ING5 epigenetic regulator confirms roles in stem cell maintenance and tumor suppression in vivo.PloS one · 2025Article
- Silencing DOCK2 Attenuates Cardiac Fibrosis Following Myocardial Infarction in Mice Via Targeting PI3K/Akt and Wnt/β-Catenin Pathways.Journal of cardiovascular translational research · 2024Article
- Non-immune factors cause prolonged myofibroblast phenotype in implanted synthetic heart valve scaffolds.Applied materials today · 2024Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adult mammalian heart is thought to be a terminally differentiated organ given the postmitotic nature of cardiomyocytes. Consequently, the potential for cardiac repair through cardiomyocyte proliferation is extremely limited. Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor that is required for embryonic heart development. In this study we investigated the role of LRP6 in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice. Cardiomyocyte-specific deletion of Lrp6 in the mouse heart induced a robust regenerative response after myocardial infarction (MI), led to reduced MI area and improvement in left ventricular systolic function. In vivo genetic lineage tracing revealed that the newly formed cardiomyocytes in Lrp6-deficient mouse hearts after MI were mainly derived from resident cardiomyocytes. Furthermore, we found that the pro-proliferative effect of Lrp6 deficiency was mediated by the ING5/P21 signaling pathway. Gene therapy using the adeno-associated virus (AAV)9 miRNAi-Lrp6 construct promoted the repair of heart injury in mice. Lrp6 deficiency also induced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our study identifies LRP6 as a critical regulator of cardiomyocyte proliferation, which may lead to the development of a novel molecular strategy to promote myocardial regeneration and repair.
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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.