The role of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ref-1) in vascular smooth muscle cells has yet to be clearly elucidated. Therefore, we attempted to determine the roles of Ref-1 in the migration induced by platelet-derived growth factor (PDGF)-BB and in its signaling in rat aortic smooth muscle cells (RASMCs). Cellular migration, superoxide (O(2)(-*)) production, Rac-1 activity, and neointima formation were determined in cells transfected with adenoviruses encoding for Ref-1 (AdRef-1) and small interference RNA of Ref-1. Overexpression of Ref-1 induced by treatment with RASMCs coupled with AdRef-1 inhibited the migration induced by PDGF-BB. PDGF-BB also increased the phosphorylation of the PDGFbeta receptor, spleen tyrosine kinase (Syk), mitogen-activated protein kinase, and heat shock protein 27, but these increases were significantly inhibited by AdRef-1 treatment. PDGF-BB increased O(2)(-*) production and Rac-1 activity, and these were diminished in cells transfected with AdRef-1. In contrast, RASMC migration, phosphorylation of Syk and O(2)(-*) production in response to PDGF-BB were increased by the knock down of Ref-1 with small interference RNA. The phosphorylation of PDGFbeta receptor in response to PDGF-BB was inhibited completely by the Syk inhibitor and was partly attenuated by a NADPH oxidase inhibitor. PDGF-BB increased the sprout outgrowth of the aortic ring ex vivo, which was inhibited in the AdRef-1-infected RASMCs as compared with the controls. Balloon injury-induced neointimal formation was significantly attenuated by the gene transfer of AdRef-1. These results indicate that Ref-1 inhibits the PDGF-mediated migration signal via the inhibition of reactive oxygen species-mediated Syk activity in RASMCs.
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http://dx.doi.org/10.1161/CIRCRESAHA.108.178699 | DOI Listing |
Oncoimmunology
December 2025
Department of Cancer Immunology, Oslo University Hospital, Oslo, Norway.
The immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treatment response, adverse events and overall survival (OS) in patients with metastatic melanoma undergoing ipilimumab monotherapy. A cohort of 148 patients was examined, with plasma samples collected prior to treatment initiation and at the end of the first and second treatment cycles.
View Article and Find Full Text PDFJ Diabetes Metab Disord
June 2025
Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, P.O. Box 566, Irbid, 21163 Jordan.
Objectives: Diabetes mellitus (DM) contributes to the development and progression of nephropathy and kidney diseases. Statins are known to have anti-inflammatory and antifibrotic effects. We aimed to test the short-term effect of atorvastatin on renal biomarkers of oxidative damage, inflammation, and fibrosis in a rat model of streptozotocin-induced DM.
View Article and Find Full Text PDFTissue Cell
December 2024
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China. Electronic address:
Introduction: The phenotypic transition of vascular smooth muscle cells (VSMCs) from a quiescent, contractile type to a secretory phenotype with high proliferation and mobility is a key event in vascular remodeling. PF-477736 is an ATP-competitive inhibitor of Chk1 which induces the accumulation of DNA damage by increasing the level of replicative stress, and ultimately inhibiting cell proliferation or causing cell death. Although this compound has been utilized as an anti-tumor drug, its role in vascular remodeling remains unclear.
View Article and Find Full Text PDFFood Funct
December 2024
Department of Heart Center, The Third Central Hospital of, Tianjin, 300170, China.
Despite the significant alleviation of clinical cardiovascular diseases through appropriate interventional treatments, the recurrence of vascular restenosis necessitating reoperation remains a substantial challenge impacting patient prognosis. Plant-derived exosome-like nanovesicles (PELNs) are integral to interspecies cellular communication, with their functions and potential applications garnering significant attention from the research community. This study extracted -derived exosome-like nanovesicles (SL-ELNs) and demonstrated their inhibition of PDGF-BB-induced proliferation, migration, and phenotypic transformation of vascular smooth muscle cells (VSMCs).
View Article and Find Full Text PDFActa Pharmacol Sin
December 2024
Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230601, China.
Vascular smooth muscle cell (VSMC) phenotype transformation significantly contributes to vascular intimal hyperplasia. However, effective preventive and therapeutic measures are lacking. Colchicine, a binary alkaloid derived from Colchicum autumnale, is traditionally used for treating inflammatory diseases.
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