Inhibition of PCSK9 Protects against Cerebral Ischemia‒Reperfusion Injury via Attenuating Microcirculatory Dysfunction

Feigin VL, Brainin M, Norrving B, Martins S, Sacco RL, Hacke W, Fisher M, Pandian J, Lindsay P (2022) World Stroke Organization (WSO): global stroke fact sheet 2022. Int J Stroke 17:18–29. https://doi.org/10.1177/17474930211065917

Article  PubMed  Google Scholar 

Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B et al (2019) Guidelines for the early management of patients with Acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of Acute ischemic stroke: a Guideline for Healthcare professionals from the American Heart Association/American Stroke Association. Stroke 50:e344–e418. https://doi.org/10.1161/STR.0000000000000211

Article  PubMed  Google Scholar 

Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA et al (2016) Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 387:1723–1731. https://doi.org/10.1016/S0140-6736(16)00163-X

Article  PubMed  Google Scholar 

Eltzschig HK, Eckle T (2011) Ischemia and reperfusion–from mechanism to translation. Nat Med 17:1391–1401. https://doi.org/10.1038/nm.2507

Article  PubMed  CAS  Google Scholar 

Przykaza L (2021) Understanding the connection between common stroke comorbidities, their Associated inflammation, and the course of the cerebral Ischemia/Reperfusion Cascade. Front Immunol 12. https://doi.org/10.3389/fimmu.2021.782569

Erdener SE, Tang J, Kilic K, Postnov D, Giblin JT, Kura S, Chen IA, Vayisoglu T, Sakadzic S, Schaffer CB, Boas DA (2021) Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury: a hyperacute role for neutrophils in persistent traffic jams. J Cereb Blood Flow Metab 41:236–252. https://doi.org/10.1177/0271678X20914179

Article  PubMed  CAS  Google Scholar 

Renu A, Millan M, San Roman L, Blasco J, Marti-Fabregas J, Terceno M, Amaro S, Serena J, Urra X, Laredo C et al (2022) Effect of intra-arterial alteplase vs Placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion Acute ischemic stroke: the CHOICE Randomized Clinical Trial. JAMA 327:826–835. https://doi.org/10.1001/jama.2022.1645

Article  PubMed  CAS  Google Scholar 

Arsava EM, Arat A, Topcuoglu MA, Peker A, Yemisci M, Dalkara T (2018) Angiographic microcirculatory obstructions distal to occlusion signify poor outcome after Endovascular Treatment for Acute ischemic stroke. Transl Stroke Res 9:44–50. https://doi.org/10.1007/s12975-017-0562-2

Article  PubMed  CAS  Google Scholar 

Cho TH, Nighoghossian N, Mikkelsen IK, Derex L, Hermier M, Pedraza S, Fiehler J, Ostergaard L, Berthezene Y, Baron JC (2015) Reperfusion within 6 hours outperforms recanalization in predicting penumbra salvage, lesion growth, final infarct, and clinical outcome. Stroke 46:1582–1589. https://doi.org/10.1161/STROKEAHA.114.007964

Article  PubMed  Google Scholar 

Xu XR, Zhang D, Oswald BE, Carrim N, Wang X, Hou Y, Zhang Q, Lavalle C, McKeown T, Marshall AH, Ni H (2016) Platelets are versatile cells: new discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond. Crit Rev Clin Lab Sci 53:409–430. https://doi.org/10.1080/10408363.2016.1200008

Article  PubMed  CAS  Google Scholar 

Xu XR, Carrim N, Neves MA, McKeown T, Stratton TW, Coelho RM, Lei X, Chen P, Xu J, Dai X et al (2016) Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies. Thromb J 14:29. https://doi.org/10.1186/s12959-016-0100-6

Article  PubMed  PubMed Central  CAS  Google Scholar 

Qiao J, Arthur JF, Gardiner EE, Andrews RK, Zeng L, Xu K (2018) Regulation of platelet activation and thrombus formation by reactive oxygen species. Redox Biol 14:126–130. https://doi.org/10.1016/j.redox.2017.08.021

Article  PubMed  CAS  Google Scholar 

Iadecola C, Buckwalter MS, Anrather J (2020) Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest 130:2777–2788. https://doi.org/10.1172/JCI135530

Article  PubMed  PubMed Central  CAS  Google Scholar 

Taskiran-Sag A, Yemisci M, Gursoy-Ozdemir Y, Erdener SE, Karatas H, Yuce D, Dalkara T (2018) Improving Microcirculatory Reperfusion reduces Parenchymal Oxygen Radical formation and provides neuroprotection. Stroke 49:1267–1275. https://doi.org/10.1161/STROKEAHA.118.020711

Article  PubMed  CAS  Google Scholar 

Sundararaman SS, Doring Y, van der Vorst EPC (2021) PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology. Biomedicines 9.https://doi.org/10.3390/biomedicines9070793

Klein-Szanto AJP, Bassi DE (2019) Keep recycling going: new approaches to reduce LDL-C. Biochem Pharmacol 164:336–341. https://doi.org/10.1016/j.bcp.2019.04.003

Article  PubMed  CAS  Google Scholar 

Urban D, Poss J, Bohm M, Laufs U (2013) Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol 62:1401–1408. https://doi.org/10.1016/j.jacc.2013.07.056

Article  PubMed  CAS  Google Scholar 

Koren MJ, Sabatine MS, Giugliano RP, Langslet G, Wiviott SD, Ruzza A, Ma Y, Hamer AW, Wasserman SM, Raal FJ (2019) Long-term efficacy and safety of Evolocumab in patients with hypercholesterolemia. J Am Coll Cardiol 74:2132–2146. https://doi.org/10.1016/j.jacc.2019.08.1024

Article  PubMed  CAS  Google Scholar 

Blom DJ, Harada-Shiba M, Rubba P, Gaudet D, Kastelein JJP, Charng MJ, Pordy R, Donahue S, Ali S, Dong Y et al (2020) Efficacy and safety of Alirocumab in adults with homozygous familial hypercholesterolemia: the ODYSSEY HoFH Trial. J Am Coll Cardiol 76:131–142. https://doi.org/10.1016/j.jacc.2020.05.027

Article  PubMed  CAS  Google Scholar 

Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM et al (2015) Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 372:1500–1509. https://doi.org/10.1056/NEJMoa1500858

Article  PubMed  CAS  Google Scholar 

Giugliano RP, Pedersen TR, Saver JL, Sever PS, Keech AC, Bohula EA, Murphy SA, Wasserman SM, Honarpour N, Wang H et al (2020) Stroke Prevention with the PCSK9 (Proprotein Convertase Subtilisin-Kexin type 9) inhibitor Evolocumab added to statin in high-risk patients with stable atherosclerosis. Stroke 51:1546–1554. https://doi.org/10.1161/STROKEAHA.119.027759

Article  PubMed  CAS  Google Scholar 

Zeng J, Tao J, Xi L, Wang Z, Liu L (2021) PCSK9 mediates the oxidative low–density lipoprotein–induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway. Int J Mol Med 47. https://doi.org/10.3892/ijmm.2021.4886

Wang Q, Zheng B, Chen P, Lei Y (2022) Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease. Open Med (Wars) 17:185–190. https://doi.org/10.1515/med-2021-0400

Article  PubMed  CAS  Google Scholar 

Song L, Zhao X, Chen R, Li J, Zhou J, Liu C, Zhou P, Wang Y, Chen Y, Zhao H, Yan H (2022) Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes. Cardiovasc Diabetol 21. https://doi.org/10.1186/s12933-022-01519-3

Cammisotto V, Pastori D, Nocella C, Bartimoccia S, Castellani V, Marchese C, Scavalli AS, Ettorre E, Viceconte N, Violi F et al (2020) PCSK9 regulates Nox2-Mediated platelet activation via CD36 receptor in patients with Atrial Fibrillation. Antioxid (Basel) 9. https://doi.org/10.3390/antiox9040296

Barale C, Bonomo K, Frascaroli C, Morotti A, Guerrasio A, Cavalot F, Russo I (2020) Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: a 12-month follow-up. Nutr Metab Cardiovasc Dis 30:282–291. https://doi.org/10.1016/j.numecd.2019.09.012

Article  PubMed  CAS  Google Scholar 

Qi Z, Hu L, Zhang J, Yang W, Liu X, Jia D, Yao Z, Chang L, Pan G, Zhong H et al (2021) PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) enhances platelet activation, thrombosis, and myocardial infarct expansion by binding to platelet CD36. Circulation 143:45–61. https://doi.org/10.1161/CIRCULATIONAHA.120.046290

Article  PubMed  CAS  Google Scholar 

Wang X, Li X, Liu S, Brickell AN, Zhang J, Wu Z, Zhou S, Ding Z (2020) PCSK9 regulates pyroptosis via mtDNA damage in chronic myocardial ischemia. Basic Res Cardiol 115:66. https://doi.org/10.1007/s00395-020-00832-w

Article  PubMed  CAS  Google Scholar 

Sun R, Peng M, Xu P, Huang F, Xie Y, Li J, Hong Y, Guo H, Liu Q, Zhu W (2020) Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia/reperfusion injury. J Neuroinflammation 17:330. https://doi.org/10.1186/s12974-020-01988-x

Zhang Z, Shen C, Fang M, Han Y, Long C, Liu W, Yang M, Liu M, Zhang D, Cao Q et al (2022) Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke. Cell Mol Life Sci 79:240. https://doi.org/10.1007/s00018-022-04257-7

Article  PubMed  PubMed Central  CAS  Google Scholar 

Xu P, Liu Q, Xie Y, Shi X, Li Y, Peng M, Guo H, Sun R, Li J, Hong Y et al (2018) Breast cancer susceptibility protein 1 (BRCA1) rescues neurons from cerebral ischemia/reperfusion injury through NRF2-mediated antioxidant pathway. Redox Biol 18:158–172.

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