دورية أكاديمية
Antibody-mediated PCSK9 neutralization worsens outcome after bare-metal stent implantation in mice.
| العنوان: | Antibody-mediated PCSK9 neutralization worsens outcome after bare-metal stent implantation in mice. |
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| المؤلفون: | Puspitasari YM; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland., Ministrini S; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Internal Medicine, Angiology and Atherosclerosis, Department of Medicine and Surgery, University of Perugia, Perugia, Italy., Liberale L; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy., Vukolic A; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland., Baumann-Zumstein P; Biotronik AG, Vascular Interventions, Bülach, Switzerland., Holy EW; Department of Angiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Montecucco F; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy., Lüscher TF; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Cardiology, Royal Brompton & Harefield Hospitals and National Heart & Lung Institute, Imperial College, London, United Kingdom., Camici GG; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Research and Education, University Hospital Zurich, Zurich, Switzerland. Electronic address: giovanni.camici@uzh.ch. |
| المصدر: | Vascular pharmacology [Vascul Pharmacol] 2023 Dec; Vol. 153, pp. 107170. Date of Electronic Publication: 2023 Aug 31. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 101130615 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3649 (Electronic) Linking ISSN: 15371891 NLM ISO Abbreviation: Vascul Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Elsevier Science, c2002- |
| مواضيع طبية MeSH: | Proprotein Convertase 9*/metabolism , Percutaneous Coronary Intervention*/adverse effects, Humans ; Animals ; Mice ; Hyperplasia/etiology ; Endothelial Cells/metabolism ; Stents |
| مستخلص: | Aims: Despite advances in pharmacotherapy and device innovation, in-stent restenosis (ISR) and stent thrombosis (ST) remain serious complications following percutaneous coronary intervention (PCI) procedure with stent implantation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme involved in plasma cholesterol homeostasis and recently emerged as a therapeutic target for hypercholesterolemia. Antibody-based PCSK9 inhibition is increasingly used in different subsets of patients, including those undergoing PCI. However, whether PCSK9 inhibition affects outcome after stent implantation remains unknown. Methods and Results: 12 to 14 weeks old C57Bl/6 mice underwent carotid artery bare-metal stent implantation. Compared to sham intervention, stent implantation was associated with increased expression of several inflammatory mediators, including PCSK9. The increase in PCSK9 protein expression was confirmed in the stented vascular tissue, but not in plasma. To inhibit PCSK9, alirocumab was administered weekly to mice before stent implantation. After 6 weeks, histological examination revealed increased intimal hyperplasia in the stented segment of alirocumab-treated animals compared to controls. In vitro, alirocumab promoted migration and inhibited the onset of senescence in primary human vascular smooth muscle cells (VSMC). Conversely, it blunted the migration and increased the senescence of endothelial cells (EC). Conclusion: Antibody-based PCSK9 inhibition promotes in-stent intimal hyperplasia and blunts vascular healing by increasing VSMC migration, while reducing that of EC. This effect is likely mediated, at least in part, by a differential effect on VSMC and EC senescence. The herein-reported data warrant additional investigations concerning the use of PCSK9 inhibitors in patients undergoing PCI with stent implantation. Competing Interests: Declaration of Competing Interest LL and GGC are coinventors on the International Patent WO/2020/226993 filed in April 2020. The patent relates to the use of antibodies which specifically bind IL-1α to reduce various sequelae of ischemia-reperfusion injury to the central nervous system. GGC is a consultant to Sovida solutions limited. GGC received research grant from BIOTRONIK for a project unrelated to this article. PB is an employee of BOTRONIK. TFL has no conflicts related to this manuscript. Outside the work he received unrestricted research and education grants from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daichi-Sankyo, Novartis, Roche Diagnostics, Sanofi, Servier and Vifor. LL reports speaker fees outside of this work from Daichi-Sankyo. The other authors report no conflict of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | 310030_197510 Switzerland SNSF_ Swiss National Science Foundation |
| فهرسة مساهمة: | Keywords: Angioplasty; Bare metal stent; Intimal hyperplasia; PCSK9; Percutaneous coronary intervention |
| المشرفين على المادة: | EC 3.4.21.- (PCSK9 protein, human) EC 3.4.21.- (Proprotein Convertase 9) |
| تواريخ الأحداث: | Date Created: 20230902 Date Completed: 20231216 Latest Revision: 20240430 |
| رمز التحديث: | 20240430 |
| DOI: | 10.1016/j.vph.2023.107170 |
| PMID: | 37659608 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1879-3649 |
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| DOI: | 10.1016/j.vph.2023.107170 |