ArticleArteriosclerosis, thrombosis, and vascular biology2011
RAGE-dependent activation of the oncoprotein Pim1 plays a critical role in systemic vascular remodeling processes.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Association of RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies.Medical oncology (Northwood, London, England) · 2015Pooled it
- Metabolic reprogramming and epigenetic effects due to reducing sugars and glycation products in cancer.Frontiers in epigenetics and epigenomics · 2025Review
- Nε-Carboxymethyl-Lysine Mediates Vascular Calcification in Diabetes Caused by Impaired Osteoclastic Resorption Activity Through NFATc1-GNPTAB.Journal of cardiovascular translational research · 2023Article
- Advanced glycation end products regulate the receptor of AGEs epigenetically.Frontiers in cell and developmental biology · 2023Article
- PathwayKO: An integrated platform for deciphering the systems-level signaling pathways.Frontiers in immunology · 2023Article
- Transcriptional analysis of lung fibroblasts identifies PIM1 signaling as a driver of aging-associated persistent fibrosis.JCI insight · 2022Article
- Review
- Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response.International journal of molecular sciences · 2022Article
- Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis.Frontiers in endocrinology · 2022Review
- Glycation and Glycosylation in Cardiovascular Remodeling: Focus on Advanced Glycation End Products and O-Linked Glycosylations as Glucose-Related Pathogenetic Factors and Disease Markers.Journal of clinical medicine · 2021Review
- Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Soluble Receptor for Advanced Glycation End Products (sRAGE) Is a Sensitive Biomarker in Human Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Molecular and Genetic Profiling for Precision Medicines in Pulmonary Arterial Hypertension.Cells · 2021Review
- Review
- HIMF (Hypoxia-Induced Mitogenic Factor) Signaling Mediates the HMGB1 (High Mobility Group Box 1)-Dependent Endothelial and Smooth Muscle Cell Crosstalk in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Mechanism of Development of Atherosclerosis and Cardiovascular Disease in Diabetes Mellitus.Journal of atherosclerosis and thrombosis · 2018Review
- Genetic Variants of the Receptor for Advanced Glycation End-products in Susceptibility to Type 2 Diabetes Mellitus in Primary Hypertensive Patients.Scientific reports · 2017Article
- ADAMTS5 Deficiency in Calcified Aortic Valves Is Associated With Elevated Pro-Osteogenic Activity in Valvular Interstitial Cells.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis.Cell death & disease · 2017Article
- MiR-328 targeting PIM-1 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in PDGFBB signaling pathway.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectiveVascular remodeling diseases (VRD) are mainly characterized by inflammation and a vascular smooth muscle cells (VSMCs) proproliferative and anti-apoptotic phenotype. Recently, the activation of the advanced glycation endproducts receptor (RAGE) has been shown to promote VSMC proliferation and resistance to apoptosis in VRD in a signal transducer and activator of transcription (STAT)3-dependant manner. Interestingly, we previously described in both cancer and VRD that the sustainability of this proproliferative and antiapoptotic phenotype requires activation of the transcription factor NFAT (nuclear factor of activated T-cells). In cancer, NFAT activation is dependent of the oncoprotein provirus integration site for Moloney murine leukemia virus (Pim1), which is regulated by STAT3 and activated in VRD. Therefore, we hypothesized that RAGE/STAT3 activation in VSMC activates Pim1, promoting NFAT and thus VSMC proliferation and resistance to apoptosis. Methods/Results- In vitro, freshly isolated human carotid VSMCs exposed to RAGE activator Nε-(carboxymethyl)lysine (CML) for 48 hours had (1) activated STAT3 (increased P-STAT3/STAT3 ratio and P-STAT3 nuclear translocation); (2) increased STAT3-dependent Pim1 expression resulting in NFATc1 activation; and (3) increased Pim1/NFAT-dependent VSMC proliferation (PCNA, Ki67) and resistance to mitochondrial-dependent apoptosis (TMRM, Annexin V, TUNEL). Similarly to RAGE inhibition (small interfering RNA [siRNA]), Pim1, STAT3 and NFATc1 inhibition (siRNA) reversed these abnormalities in human carotid VSMC. Moreover, carotid artery VSMCs isolated from Pim1 knockout mice were resistant to CML-induced VSMC proliferation and resistance to apoptosis. In vivo, RAGE inhibition decreases STAT3/Pim1/NFAT activation, reversing vascular remodeling in the rat carotid artery-injured model.
conclusionsRAGE activation accounts for many features of VRD including VSMC proliferation and resistance to apoptosis by the activation of STAT3/Pim1/NFAT axis. Molecules aimed to inhibit RAGE could be of a great therapeutic interest for the treatment of VRD.
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