PERK Inhibition Mitigates Restenosis and Thrombosis
| العنوان: | PERK Inhibition Mitigates Restenosis and Thrombosis |
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| المؤلفون: | Yitao Huang, Shahid M Nimjee, Go Urabe, Debra G Wheeler, David J. Dornbos, Bowen Wang, Allyson Huttinger, Guojun Chen, Mengxue Zhang, Lian-Wang Guo, K. Craig Kent, Shaoqin Gong |
| المصدر: | JACC: Basic to Translational Science |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, STAT3, signal transducer and activator of transcription 3, Cell, SMC, smooth muscle cell, DMSO, dimethyl sulfoxide, 030204 cardiovascular system & hematology, ATF, activating transcription factor, PDGF, platelet-derived growth factor, PRECLINICAL RESEARCH, 0302 clinical medicine, siRNA, small interfering ribonucleic acid, Restenosis, PDGF-BB, platelet-derived growth factor with 2 B subunits, I/M, intima to media, GFP, green fluorescent protein, Neointimal hyperplasia, TNF, tumor necrosis factor, Ad, adenovirus, Hyperplasia, Thrombosis, endothelial cells, smooth muscle cells, 3. Good health, Endothelial stem cell, IRE1, inositol-requiring kinase 1, medicine.anatomical_structure, SMA, smooth muscle actin, Cardiology and Cardiovascular Medicine, PERK, endocrine system, Thrombogenicity, IEL, internal elastic lamina, CHOP, CCAAT-enhancer-binding protein homologous protein, eIF2, eukaryotic translation initiation factor 2, ER, endoplasmic reticulum, MRTF-A, myocardin related transcription factor A, restenosis, IH, intimal hyperplasia, 03 medical and health sciences, Tissue factor, FBS, fetal bovine serum, medicine, DES, drug-eluting stents, thrombosis, EC, endothelial cell, business.industry, PERK, protein kinase RNA-like endoplasmic reticulum kinase, medicine.disease, SRF, serum response factor, 030104 developmental biology, Cancer research, business, HA, hemagglutinin |
| الوصف: | Visual Abstract Highlights • Drug-eluting stents impede neointimal smooth muscle cell hyperplasia but exacerbate endothelial cell dysfunction and thrombogenicity. It has been a challenge to identify a common target to inhibit both. Findings in this study suggest PERK as such a target. • A PERK inhibitor administered either via an endovascular (in biomimetic nanocarriers) or perivascular (in hydrogel) route effectively mitigated neointimal hyperplasia in rats. • Oral gavage of the PERK inhibitor partially preserved the normal blood flow in a mouse model of induced thrombosis. • Dampening PERK activity inhibited STAT3 while activating SRF in smooth muscle cells, and also reduced prothrombogenic tissue factor and growth impairment of endothelial cells. Summary Developing endothelial-protective, nonthrombogenic antirestenotic treatments has been a challenge. A major hurdle to this has been the identification of a common molecular target in both smooth muscle cells and endothelial cells, inhibition of which blocks dysfunction of both cell types. The authors’ findings suggest that the PERK kinase could be such a target. Importantly, PERK inhibition mitigated both restenosis and thrombosis in preclinical models, implicating a low-thrombogenic antirestenotic paradigm. |
| تدمد: | 2452-302X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::687fd944746d5484e3fd724b4e1ee496Test https://doi.org/10.1016/j.jacbts.2019.12.005Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....687fd944746d5484e3fd724b4e1ee496 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2452302X |
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