ArticleStem cell research & therapy2016
C-reactive protein can upregulate VEGF expression to promote ADSC-induced angiogenesis by activating HIF-1α via CD64/PI3k/Akt and MAPK/ERK signaling pathways.
Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- FGF-23 as a Biomarker for Carotid Plaque Vulnerability: A Systematic Review.Medical sciences (Basel, Switzerland) · 2025Pooled it
- Effects of advanced glycation end products (AGEs) on the differentiation potential of primary stem cells: a systematic review.Stem cell research & therapy · 2023Pooled it
- The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients: a double-blinded randomized clinical trial.Nutrition & diabetes · 2024Trial
- Elevated baseline C-reactive protein is associated with treatment failure and shorter survival after Yttrium-90 radioembolization in hepatocellular carcinoma.Annals of nuclear medicine · 2026Article
- Proteomic Changes in Patients with LADA-Type Diabetes: Prospects for Diagnostic Biomarkers.International journal of molecular sciences · 2026Review
- Systemic Inflammation Modifies the Efficacy of Bevacizumab Added to Atezolizumab Plus Chemotherapy for Advanced Non-Squamous Non-Small Cell Lung Cancer: A Multicenter Retrospective Study.Thoracic cancer · 2026Article
- Differentiated associations of inflammatory indices with laboratory-defined organ injury/involvement and hospitalization length in pediatric respiratory tract infections.Frontiers in pediatrics · 2026Article
- Lymphocyte-to-C-reactive protein ratio predicts prognosis in unresectable locally advanced non-small cell lung cancer patients.Annals of medicine · 2025Article
- Evaluating the CRP Interactome: Insights into Possible Novel Roles in Cellular Signaling and Tumorigenicity.Current issues in molecular biology · 2025Review
- C-reactive protein promotes diabetic kidney disease via Smad3-mediated NLRP3 inflammasome activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Redefining CRP in tissue injury and repair: more than an acute pro-inflammatory mediator.Frontiers in immunology · 2025Review
- Characteristics of the tumor microenvironment and potential immunotherapy strategies in renal cell carcinoma.Frontiers in immunology · 2025Review
- Identification of serum biomarkers associated with microvascular functions in a long-term high-fat diet-induced obesity rat model.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Human platelet lysate enhances small lipid droplet accumulation of human MSCs through MAPK phosphorylation.Stem cell research & therapy · 2024Article
- Review
- Advances in electroactive biomaterials: Through the lens of electrical stimulation promoting bone regeneration strategy.Journal of orthopaedic translation · 2024Review
- Fucoidan promotes angiogenesis and accelerates wound healing through AKT/Nrf2/HIF-1α signalling pathway.International wound journal · 2023Article
- Obesity and prostate cancer - microenvironmental roles of adipose tissue.Nature reviews. Urology · 2023Review
- C-Reactive Protein in Atherosclerosis-More than a Biomarker, but not Just a Culprit.Reviews in cardiovascular medicine · 2023Review
- Increased interleukin-6/C-reactive protein levels are associated with the upregulation of the adenosine pathway and serve as potential markers of therapeutic resistance to immune checkpoint inhibitor-based therapies in non-small cell lung cancer.Journal for immunotherapy of cancer · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProliferation of the vasa vasorum has been implicated in the pathogenesis of atherosclerosis, and the vasa vasorum is closely associated with resident stem cells within the vasculature. C-reactive protein (CRP) is positively correlated with cardiovascular disease risk, and our previous study demonstrated that it induces inflammatory reactions of perivascular adipose tissue by targeting adipocytes.
methodsHere we investigated whether CRP affected the proliferation and proangiogenic paracrine activity of adipose-derived stem cells (ADSCs), which may contribute to vasa vasorum angiogenesis.
resultsWe found that CRP did not affect ADSC apoptosis, cell cycle, or proliferation but did increase their migration by activating the PI3K/Akt pathway. Our results demonstrated that CRP can upregulate vascular endothelial growth factor-A (VEGF-A) expression by activating hypoxia inducible factor-1α (HIF-1α) in ADSCs, which significantly increased tube formation on Matrigel and functional vessels in the Matrigel plug angiogenesis assay. The inhibition of CRP-activated phosphorylation of ERK and Akt can suppress CRP-stimulated HIF-1α activation and VEGF-A expression. CRP can also stimulate proteolytic activity of matrix metalloproteinase-2 in ADSCs. Furthermore, CRP binds activating CD64 on ADSCs, rather than CD16/32.
conclusionOur findings implicate that CRP might play a role in vasa vasorum growth by activating the proangiogenic activity of ADSCs.
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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.