المؤلفون: Akagi, Daisuke, Chen, Mian, Toy, Robert, Chatterjee, Anuran, Conte, Michael S

المصدر: The FASEB Journal. 29(6)

مصطلحات موضوعية: Atherosclerosis, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Animals, Carotid Arteries, Cell Movement, Cell Proliferation, Cells, Cultured, Cytokines, Docosahexaenoic Acids, Gene Expression, Hyperplasia, Immunohistochemistry, Injections, Intraperitoneal, Ki-67 Antigen, Male, Mice, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Neointima, Neutrophil Infiltration, Reverse Transcriptase Polymerase Chain Reaction, Superoxides, Tumor Necrosis Factor-alpha, Tunica Intima, Vascular Remodeling, neointimal hyperplasia, inflammation, vascular remodeling, fatty acid, Biochemistry and Cell Biology, Physiology, Medical Physiology, Biochemistry & Molecular Biology

الوصف: Vascular injury induces a potent inflammatory response that influences vessel remodeling and patency, limiting long-term benefits of cardiovascular interventions such as angioplasty. Specialized proresolving lipid mediators (SPMs) derived from ω-3 polyunsaturated fatty acids [eicosapentaenoic acid and docosahexaenoic acid (DHA)] orchestrate resolution in diverse settings of acute inflammation. We hypothesized that systemic administration of DHA-derived SPMs [resolvin D2 (RvD2) and maresin 1 (MaR1)] would influence vessel remodeling in a mouse model of arterial neointima formation (carotid ligation). In vitro, SPM treatment inhibited mouse aortic smooth muscle cell migration (IC₅₀ ≅ 1 nM) to a PDGF gradient and reduced TNF-α-stimulated p65 translocation, superoxide production, and proinflammatory gene expression (MCP-1). In vivo, adult FVB mice underwent unilateral carotid artery ligation with administration of RvD2, MaR1, or vehicle (100 ng by intraperitoneal injection at 0, 1, 3, 5, and 7 d after ligation). In ligated carotid arteries at 4 d, SPM treatment was associated with reduced cell proliferation and neutrophil and macrophage recruitment and increased polarization of M2 macrophages in the arterial wall. Neointimal hyperplasia (at 14 d) was notably attenuated in RvD2 (62%)- and MaR1 (67%)-treated mice, respectively. Modulation of resolution pathways may offer new opportunities to regulate the vascular injury response and promote vascular homeostasis.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9cb0m3v3Test

المؤلفون: Xing-Jie Yin, Chun Zhang, Anni Song, Xian-Fang Meng, Hui Tang, Pan Gao

المصدر: The FASEB Journal. 35

مصطلحات موضوعية: Male, Small interfering RNA, Vascular smooth muscle, Intimal hyperplasia, Myocytes, Smooth Muscle, Biochemistry, Muscle, Smooth, Vascular, Mice, Cell Movement, In vivo, Neointima, Genetics, medicine, Animals, Humans, Molecular Biology, Mitosis, Cells, Cultured, Cell Proliferation, Neointimal hyperplasia, Hyperplasia, Chemistry, Cell growth, musculoskeletal system, medicine.disease, In vitro, Mice, Inbred C57BL, Mad2 Proteins, cardiovascular system, Cancer research, Kidney Failure, Chronic, Biotechnology

الوصف: The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential events in venous neointimal hyperplasia (VNH), a culprit of arteriovenous fistula (AVF) malfunction. Mitotic arrest-deficient protein 2B (MAD2B) is a critical regulator of cell proliferation and differentiation in many scenarios. To address the role of MAD2B in VSMCs proliferation and migration during VNH, AVFs from patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) mice were used to evaluate MAD2B expression. In cultured VSMCs treated with platelet-derived growth factor-BB (PDGF-BB), the effect of MAD2B on VSMCs proliferation and migration was detected by cell counting kit-8 (CCK8) assay, immunofluorescence, wound-healing scratch and transwell assays. Besides, we exploited different small interfering RNAs (siRNAs) to explore the potential mechanisms in the issue. Furthermore, rapamycin was applied to reveal whether MAD2B-associated pathways were involved in its inhibitory effect on VSMCs proliferation and migration. Accordingly, we found that MAD2B expression was enhanced in AVFs from patients with ESRD, CKD mice and VSMCs stimulated by PDGF-BB. Meanwhile, inhibition of MAD2B alleviated VSMCs proliferation and migration while the number of ski-related novel gene (SnoN)-positive VSMCs was also increased in vivo and in vitro. Moreover, gene deletion of MAD2B decreased the level of SnoN protein in PDGF-BB-stimulated VSMCs. Furthermore, rapamycin suppressed the increased expressions of MAD2B and SnoN induced by PDGF-BB. Thus, our study demonstrates that inhibition of MAD2B suppresses the proliferation and migration of VSMCs during VNH via reducing SnoN expression. Moreover, rapamycin exerts an inhibitory effect on intimal hyperplasia, possibly via the MAD2B-SnoN axis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1aac428aeb9f54e7a97a3c01d20c80caTest
https://doi.org/10.1096/fj.202100584rrTest

المؤلفون: Yujun Shen, Yuanyang Wang, Yu Yu, Ying Yu, Shumin Guo, Rui Zhang, Qiangyou Wan, Qian Liu, Jian Zhang, Guizhu Liu

المصدر: The FASEB Journal. 33:10207-10217

مصطلحات موضوعية: Male, 0301 basic medicine, Polychlorinated Dibenzodioxins, Vascular smooth muscle, Proto-Oncogene Proteins c-jun, Biochemistry, Gene Knockout Techniques, Mice, 0302 clinical medicine, Genes, Reporter, heterocyclic compounds, RNA, Small Interfering, Aorta, Neointimal hyperplasia, biology, Kinase, Chemistry, Cell Cycle, Cell cycle, Cell biology, Femoral Artery, Phenotype, Environmental Pollutants, RNA Interference, Biotechnology, Neointima, endocrine system, Myocytes, Smooth Muscle, Vascular Remodeling, 03 medical and health sciences, Cyclin D1, Genes, jun, Genetics, medicine, Animals, Humans, Gene silencing, RNA, Messenger, Molecular Biology, Hyperplasia, medicine.disease, Aryl hydrocarbon receptor, Mice, Inbred C57BL, 030104 developmental biology, Gene Expression Regulation, Receptors, Aryl Hydrocarbon, biology.protein, Endothelium, Vascular, 030217 neurology & neurosurgery

الوصف: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant that causes cardiovascular toxicity. The phenotypic transformation of vascular smooth muscle cells (VSMCs) from the contractile to the synthetic phenotype is a hallmark of vascular response to injury. However, the precise role and molecular mechanism of TCDD in vascular remodeling remains unknown. In the present study, we found that TCDD treatment promoted VSMC phenotypic transition from contractile to synthetic phenotype and exaggerated vascular neointimal hyperplasia after wire injury in mice. TCDD treatment enhanced VSMC entry into cell cycle from G0/G1 phase to S and G2/M phase. The expression of cyclin D1, cyclin-dependent kinase 4 (CDK4), and its phosphorylation were coordinately increased in response to TCDD treatment. Knocking down of aryl hydrocarbon receptor (AHR) inhibited VSMC phenotypic transition induced by TCDD and promoted S/G2 phase cell cycle arrest. TCDD treatment markedly increased oncogenic c-Jun gene expression in VSMCs. ChIP assay revealed the direct binding of AHR on the promoter of c-Jun to up-regulate the mRNA expression of c-Jun. Silencing of c-Jun gene enhanced the expression of p53 and p21, whereas attenuated the expression of CDK4 and cyclin D1 leading to the decrease in the TCDD-stimulated VSMC proliferation and synthetic phenotype transition in vitro. In vivo study showed that genetic ablation of c-Jun in VSMCs restricted injury-induced neointimal hyperplasia in TCDD-treated mice. Thus, TCDD exposure exaggerated injury-induced vascular remodeling by the activation of AHR and up-regulation of the expression of its target gene c-Jun, indicating that inhibition of AHR may be a promising prevention strategy for TCDD-associated cardiovascular diseases.-Guo, S., Zhang, R., Liu, Q., Wan, Q., Wang, Y., Yu, Y., Liu, G., Shen, Y., Yu, Y., Zhang, J. 2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes injury-induced vascular neointima formation in mice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1bf6f34b70eea0101d70d5e2a057d7fTest
https://doi.org/10.1096/fj.201900546rTest

المؤلفون: Lingjuan Piao, Yujun Shen, Mingjiang Zhu, Shumin Guo, Yanjun Gong, Guizhu Liu, Colin D. Funk, Shuai Yan, Jian Zhang, Ying Yu, Rui Zhang, Qian Liu, Huiyong Yin, Xinzhi Li

المصدر: The FASEB Journal. 32:5413-5425

مصطلحات موضوعية: Male, 0301 basic medicine, Neointima, Vascular smooth muscle, medicine.medical_treatment, Myocytes, Smooth Muscle, Macrophage polarization, Inflammation, Pharmacology, Biochemistry, Muscle, Smooth, Vascular, Mice, 03 medical and health sciences, Cell Movement, Genetics, medicine, Animals, Secretion, Molecular Biology, Neointimal hyperplasia, business.industry, Stent, medicine.disease, Eicosapentaenoic acid, Femoral Artery, Disease Models, Animal, 030104 developmental biology, Eicosapentaenoic Acid, medicine.symptom, business, Biotechnology

الوصف: Mechanical insults, such as stent implantation, can induce endothelial injury, vascular inflammation, and ultimately lead to vascular neointimal hyperplasia. Resolvin E1 (RvE1), derived from the ω3 fatty acid eicosapentaenoic acid, can facilitate the resolution of inflammation in many settings. We therefore aimed to determine if there was a role for RvE1 in preventing neointimal formation after arterial injury and to understand the underlying mechanisms. Vascular inflammation and neointimal hyperplasia were induced by wire injury in the femoral arteries of mice. Administration of exogenous RvE1 and endogenously generated RvE1 via dietary supplementation with eicosapentaenoic acid and aspirin markedly reduced vascular neointima formation in this model. Mechanistically, RvE1 was found to inhibit vascular neutrophil infiltration, promote macrophage polarization toward an M2-like phenotype, suppress T-cell trafficking by reducing RANTES secretion from vascular smooth muscle cells, and inhibit vascular smooth muscle cell migration. In summary, RvE1 demonstrated a protective role against vascular inflammation and remodeling in response to mechanical injury, suggesting that it may serve as an adjuvant therapeutic agent for percutaneous coronary interventions, such as stent implantation.-Liu, G., Gong, Y., Zhang, R., Piao, L., Li, X., Liu, Q., Yan, S., Shen, Y., Guo, S., Zhu, M., Yin, H., Funk, C. D., Zhang, J., Yu, Y. Resolvin E1 attenuates injury-induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::755e0d5cedd61bcabf6057b71ed857afTest
https://doi.org/10.1096/fj.201800173rTest

المؤلفون: Bowen Lou, Dong Zhou, Xiaoli Chen, Qiang Zhao, Yue Wu, Yan Zhang, Juan Zhou, Yan Liu, Yuling Tian, Zuyi Yuan, Hongjun You, Ning Guo

المصدر: The FASEB Journal. 31:5321-5331

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Intimal hyperplasia, Immunoblotting, Antigens, Differentiation, Myelomonocytic, Antineoplastic Agents, Apoptosis, Inflammation, Biochemistry, Interferon-gamma, Mice, 03 medical and health sciences, Apolipoproteins E, Antigens, CD, Neointima, Internal medicine, In Situ Nick-End Labeling, Genetics, medicine, Animals, Immunoprecipitation, Liver X receptor, Molecular Biology, Liver X Receptors, Mice, Knockout, Neointimal hyperplasia, Hyperplasia, Ubiquitin, Chemistry, Macrophages, Endoplasmic reticulum, Ubiquitination, Endoplasmic Reticulum Stress, medicine.disease, Protein Inhibitors of Activated STAT, 030104 developmental biology, Endocrinology, Cancer research, Unfolded protein response, medicine.symptom, Vidarabine, Biotechnology

الوصف: Neointimal hyperplasia is the main cause of restenosis after percutaneous coronary interventions (PCIs). Both IFN-γ and macrophages play nonredundant roles in the pathogenesis of vascular intimal hyperplasia; however, the underlying mechanisms remain elusive and must be further investigated. In mouse peritoneal macrophages, IFN-γ significantly accelerated degradation and up-regulated polyubiquitination of liver X receptor (LXR)-α. Signal transducer and activator of transcription 1 (STAT1) inhibitor, fludarabine, and PIAS1 knockdown reduced ubiquitination and increased the expression of LXR-α in IFN-γ-treated macrophages. IFN-γ also increased the expression of endoplasmic reticulum (ER) stress-related proteins, including p-PERK, p-eIIF2α, and CCAAT-enhancer-binding protein homologous protein (CHOP), as well as apoptosis of macrophages. Treatment with ER stress inhibitor, 4-phenylbutyric acid (4-PBA), and LXR agonist, T0901317 (T0), alleviated IFN-γ-induced apoptosis in macrophages. Neointimal hyperplasia was significant after carotid ligation for 4 wk in ApoE-/- mice. IFN-γ mAb, T0, and 4-PBA treatment not only significantly attenuated neointimal hyperplasia but also decreased CD68+TUNEL+ double-positive macrophages in the hyperplastic neointima. Moreover, after 4-PBA or T0 administration, the number of CD68+p-eIIF2α+ and CD68+CHOP+ double-positive cells in neointimal was also apparently decreased. Taken together, these results defined an unexpected role of IFN-γ and LXR-α in the development of neointimal hyperplasia. The PIAS1/STAT1-dependent LXR-α degradation induced by IFN-γ promoted ER stress and apoptosis in macrophages, which leads to aggravated neointimal hyperplasia. LXR agonist efficiently improved neointimal hyperplasia, which may be a promising new strategy to ameliorate restenosis and vascular remodeling after PCI.-Zhao, Q., Zhou, D., You, H., Lou, B., Zhang, Y., Tian, Y., Guo, N., Chen, X., Liu, Y., Wu, Y., Yuan, Z., Zhou, J. IFN-γ aggravates neointimal hyperplasia by inducing endoplasmic reticulum stress and apoptosis in macrophages by promoting ubiquitin-dependent liver X receptor-α degradation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::822a064532afb389a6ec264409aa55e8Test
https://doi.org/10.1096/fj.201700327rTest

المؤلفون: Anuran Chatterjee, Daisuke Akagi, Robert Toy, Michael S. Conte, Mian Chen

المصدر: The FASEB Journal. 29:2504-2513

مصطلحات موضوعية: Male, Neointima, Intimal hyperplasia, Docosahexaenoic Acids, Smooth muscle cell migration, Myocytes, Smooth Muscle, Gene Expression, Inflammation, Vascular Remodeling, Biology, Pharmacology, Biochemistry, Muscle, Smooth, Vascular, Proinflammatory cytokine, Mice, Research Communication, Cell Movement, Superoxides, Genetics, medicine, Animals, Maresin, Molecular Biology, Cells, Cultured, Cell Proliferation, Neointimal hyperplasia, Hyperplasia, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha, medicine.disease, Immunohistochemistry, Carotid Arteries, Ki-67 Antigen, Neutrophil Infiltration, Docosahexaenoic acid, Immunology, Cytokines, medicine.symptom, Tunica Intima, Injections, Intraperitoneal, Biotechnology

الوصف: Vascular injury induces a potent inflammatory response that influences vessel remodeling and patency, limiting long-term benefits of cardiovascular interventions such as angioplasty. Specialized proresolving lipid mediators (SPMs) derived from ω-3 polyunsaturated fatty acids [eicosapentaenoic acid and docosahexaenoic acid (DHA)] orchestrate resolution in diverse settings of acute inflammation. We hypothesized that systemic administration of DHA-derived SPMs [resolvin D2 (RvD2) and maresin 1 (MaR1)] would influence vessel remodeling in a mouse model of arterial neointima formation (carotid ligation). In vitro, SPM treatment inhibited mouse aortic smooth muscle cell migration (IC50 ≅ 1 nM) to a PDGF gradient and reduced TNF-α–stimulated p65 translocation, superoxide production, and proinflammatory gene expression (MCP-1). In vivo, adult FVB mice underwent unilateral carotid artery ligation with administration of RvD2, MaR1, or vehicle (100 ng by intraperitoneal injection at 0, 1, 3, 5, and 7 d after ligation). In ligated carotid arteries at 4 d, SPM treatment was associated with reduced cell proliferation and neutrophil and macrophage recruitment and increased polarization of M2 macrophages in the arterial wall. Neointimal hyperplasia (at 14 d) was notably attenuated in RvD2 (62%)- and MaR1 (67%)-treated mice, respectively. Modulation of resolution pathways may offer new opportunities to regulate the vascular injury response and promote vascular homeostasis.—Akagi, D., Chen, M., Toy, R., Chatterjee, A., Conte, M. S. Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1 attenuates intimal hyperplasia in mice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97cf4782daeaa942e46b94752a671338Test
https://doi.org/10.1096/fj.14-265363Test

المؤلفون: Yusuke Uemura, Yasuhiro Ogura, Yusuke Joki, Noriyuki Ouchi, Koji Ohashi, Toyoaki Murohara, Takashi Yamamoto, Rei Shibata, Megumi Miyabe, Kazuhiro Matsuo, Takashi Enomoto, Takahiro Kambara, Daisuke Yuasa, Yoshiyuki Kataoka

المصدر: The FASEB Journal. 27:25-33

مصطلحات موضوعية: Male, MAPK/ERK pathway, medicine.medical_specialty, Vascular smooth muscle, medicine.medical_treatment, Blotting, Western, Adipose tissue, Biochemistry, Muscle, Smooth, Vascular, Mice, Restenosis, Internal medicine, Genetics, Animals, Humans, Medicine, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Molecular Biology, Cells, Cultured, Cell Proliferation, Glycoproteins, Neointimal hyperplasia, biology, business.industry, Cell growth, Growth factor, Anatomy, medicine.disease, Recombinant Proteins, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Mice, Inbred C57BL, Endocrinology, Adipose Tissue, biology.protein, Adiponectin, Tunica Intima, business, Platelet-derived growth factor receptor, Biotechnology

الوصف: Obesity is closely associated with the progression of vascular disorders, including atherosclerosis and postangioplasty restenosis. C1q/TNF-related protein (CTRP) 9 is an adipocytokine that is down-regulated in obese mice. Here we investigated whether CTRP9 modulates neointimal hyperplasia and vascular smooth muscle cell (VSMC) proliferation in vivo and in vitro. Left femoral arteries of wild-type (WT) mice were injured by a steel wire. An adenoviral vector expressing CTRP9 (Ad-CTRP9) or β-galactosidase as a control was intravenously injected into WT mice 3 d before vascular injury. Delivery of Ad-CTRP9 significantly attenuated the neointimal thickening and the number of bromodeoxyuridine-positive proliferating cells in the injured arteries compared with that of control. Treatment of VSMCs with CTRP9 protein attenuated the proliferative and chemotactic activities induced by growth factors including platelet-derived growth factor (PDGF)-BB, and suppressed PDGF-BB-stimulated phosphorylation of ERK. CTRP9 treatment dose-dependently increased cAMP levels in VSMCs. Blockade of cAMP-PKA pathway reversed the inhibitory effect of CTRP9 on DNA synthesis and ERK phosphorylation in response to PDGF-BB. The present data indicate that CTRP9 functions to attenuate neointimal formation following vascular injury through its ability to inhibit VSMC growth via cAMP-dependent mechanism, suggesting that the therapeutic approaches to enhance CTRP9 production could be valuable for prevention of vascular restenosis after angioplasty.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdc8c7ce63ba720232e29860fdd3df58Test
https://doi.org/10.1096/fj.12-213744Test