ArticleStem cell research & therapy2021
GPR4 signaling is essential for the promotion of acid-mediated angiogenic capacity of endothelial progenitor cells by activating STAT3/VEGFA pathway in patients with coronary artery disease.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Article
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- M2 macrophages activate the IL-10/JAK2/STAT3 pathway to induce pathological microangiogenesis in the nucleus pulposus exacerbating intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2025Article
- LncRNA Growth Arrest Specific 5 Promotes Glucose Metabolism Reprogramming Via the IGF2BP1/SIX1 Axis and Inhibits Ferroptosis of Endothelial Progenitor Cells Via the miR-23a-3p/SLC7A11 Axis in Coronary Heart Disease.Anatolian journal of cardiology · 2025Article
- Biochemical impact of ALAEm supplementation in late gestation on the reproductive performance of sows.Frontiers in veterinary science · 2025Article
- Neuro-immune interactions in coronary microvascular disease: mechanisms and therapeutic prospect.Frontiers in immunology · 2025Review
- The beneficial health effects of puerarin in the treatment of cardiovascular diseases: from mechanisms to therapeutics.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Review
- Immunomodulation of Proton-activated G Protein-coupled Receptors in Inflammation.Current medical science · 2024Review
- Recent advances in acid sensing by G protein coupled receptors.Pflugers Archiv : European journal of physiology · 2024Review
- Article
- Identification of 5 hub genes for diagnosis of coronary artery disease.Frontiers in cardiovascular medicine · 2023Article
- The role of the gut microbiota in health and cardiovascular diseases.Molecular biomedicine · 2022Review
- Physiological relevance of proton-activated GPCRs.Pflugers Archiv : European journal of physiology · 2022Review
- Vascular Stem/Progenitor Cells in Vessel Injury and Repair.Frontiers in cardiovascular medicine · 2022Review
- Regulation of Endothelial Progenitor Cell Functions in Ischemic Heart Disease: New Therapeutic Targets for Cardiac Remodeling and Repair.Frontiers in cardiovascular medicine · 2022Review
- Expression Profiles of Circular RNA in Aortic Vascular Tissues of Spontaneously Hypertensive Rats.Frontiers in cardiovascular medicine · 2021Article
- Effect of Peptidylarginine Deiminase 4 on Endothelial Progenitor Cell Function in Peripheral Arterial Disease.Evidence-based complementary and alternative medicine : eCAM · 2021Article
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11 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with coronary artery disease (CAD) are characterized by a decline in vascular regeneration, which is related to the dysfunction of endothelial progenitor cells (EPCs). G-protein-coupled receptor 4 (GPR4) is a proton-sensing G-protein-coupled receptor (GPCR) that contributes to neovascularization in acidic microenvironments. However, the role of GPR4 in regulating the angiogenic capacity of EPCs from CAD patients in response to acidity generated in ischemic tissue remains completely unclear.
methodsThe angiogenic capacity of EPCs collected from CAD patients and healthy subjects was evaluated in different pH environments. The GPR4 function of regulating EPC-mediated angiogenesis was analyzed both in vitro and in vivo. The downstream mechanisms were further investigated by genetic overexpression and inhibition.
resultsAcidic environment prestimulation significantly enhanced the angiogenic capacity of EPCs from the non-CAD group both in vivo and in vitro, while the same treatment yielded the opposite result in the CAD group. Among the four canonical proton-sensing GPCRs, GPR4 displays the highest expression in EPCs. The expression of GRP4 was markedly lower in EPCs from CAD patients than in EPCs from non-CAD individuals independent of acid stimulation. The siRNA-mediated knockdown of GPR4 with subsequent decreased phosphorylation of STAT3 mimicked the impaired function of EPCs from CAD patients at pH 6.4 but not at pH 7.4. Elevating GPR4 expression restored the neovessel formation mediated by EPCs from CAD patients in an acidic environment by activating STAT3/VEGFA signaling. Moreover, the beneficial impact of GPR4 upregulation on EPC-mediated angiogenic capacity was abrogated by blockade of the STAT3/VEGFA signaling pathway.
conclusionsOur present study demonstrated for the first time that loss of GPR4 is responsible for the decline in proton sensing and angiogenic capacity of EPCs from CAD patients. Augmentation of GPR4 expression promotes the neovessel formation of EPCs by activating STAT3/VEGF signaling. This finding implicates GPR4 as a potential therapeutic target for CAD characterized by impaired neovascularization in ischemic tissues.
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