ArticleCardiovascular research2021
Role of R-spondin 2 in arterial lymphangiogenesis and atherosclerosis.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Myeloid Cell-Specific Deletion of LGR4 Suppresses Atherosclerotic Lesion Formation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Impaired lymphangiogenesis in pericoronary adipose tissue correlates with diabetes-aggravated coronary atherosclerosis.Cardiovascular diabetology · 2026Article
- Plasma R-spondin 2 levels are associated with the progression of diabetic kidney disease.Frontiers in endocrinology · 2026Article
- M2 macrophage-derived exosomes improves secondary lymphedema through cellular mitochondrial homeostasis regulation via the Keap1-Nrf2/mPTP axis.Frontiers in immunology · 2026Article
- R-spondin 2 suppresses hepatic steatosis via activation of AMPK-ACC signaling.JHEP reports : innovation in hepatology · 2025Article
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Single-Cell Transcriptomics of Human Pericarotid Lymph Nodes Indicating Stability of Carotid Atherosclerotic Plaques.Journal of the American Heart Association · 2025Article
- Extracellular matrix in vascular homeostasis and disease.Nature reviews. Cardiology · 2025Review
- Smooth muscle cell-specific CD47 deletion suppresses atherosclerosis.Life sciences · 2025Article
- Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis.International journal of molecular sciences · 2024Article
- Lymphangiogenesis: A new strategy for heart disease treatment (Review).International journal of molecular medicine · 2024Review
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease.International journal of molecular sciences · 2023Observational
- Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.Biomedicines · 2023Article
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Matricellular proteins in atherosclerosis development.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Hydrogen sulfide donor activates AKT-eNOS signaling and promotes lymphatic vessel formation.PloS one · 2023Article
- The biological functions and related signaling pathways of SPON2.Frontiers in oncology · 2023Review
- Loss of myeloid cell-specific SIRPα, but not CD47, attenuates inflammation and suppresses atherosclerosis.Cardiovascular research · 2022Article
- The role of lymphangiogenesis in cardiovascular diseases and heart transplantation.Heart failure reviews · 2022Review
Corrections and comments
- Commented on by
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
aimsImpaired lymphatic drainage of the arterial wall results in intimal lipid accumulation and atherosclerosis. However, the mechanisms regulating lymphangiogenesis in atherosclerotic arteries are not well understood. Our studies identified elevated levels of matrix protein R-spondin 2 (RSPO2) in atherosclerotic arteries. In this study, we investigated the role of RSPO2 in lymphangiogenesis, arterial cholesterol efflux into lesion-draining lymph nodes (LNs) and development of atherosclerosis. METHODS AND
resultsThe effect of RSPO2 on lymphangiogenesis was investigated using human lymphatic endothelial cells (LEC) in vitro and implanted Matrigel plugs in vivo. Cellular and molecular approaches, pharmacological agents, and siRNA silencing of RSPO2 receptor LGR4 were used to investigate RSPO2-mediated signalling in LEC. In vivo low-density lipoprotein (LDL) tracking and perivascular blockade of RSPO2-LGR4 signalling using LGR4-extracellular domain (ECD) pluronic gel in hypercholesterolemic mice were utilized to investigate the role of RSPO2 in arterial reverse cholesterol transport and atherosclerosis. Immunoblotting and imaging experiments demonstrated increased RSPO2 expression in human and mouse atherosclerotic arteries compared to non-atherosclerotic controls. RSPO2 treatment inhibited lymphangiogenesis both in vitro and in vivo. LGR4 silencing and inhibition of RSPO2-LGR4 signalling abrogated RSPO2-induced inhibition of lymphangiogenesis. Mechanistically, we found that RSPO2 suppresses PI3K-AKT-endothelial nitric oxide synthase (eNOS) signalling via LGR4 and inhibits activation of the canonical Wnt-β-catenin pathway. ApoE-/- mice treated with LGR4-ECD developed significantly less atherosclerosis compared with control treatment. Finally, increased arterial lymphatic vessel density and improved lymphatic drainage of fluorescently labelled LDL to deep cervical LNs were observed in LGR4-ECD-treated mice.
conclusionThese findings demonstrate that RSPO2 inhibits lymphangiogenesis via LGR4 and downstream impairment of AKT-eNOS-nitric oxide signalling. These results may also inform new therapeutic strategies to promote lymphangiogenesis and improve cholesterol efflux from atherosclerotic arteries.
Indexed as
Identifiers
What OpenQuestion holds
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.