Research progress on the mechanism of thromboinflammation in the occurrence and development of ischemic stroke

doi:10.11817/j.issn.1673-9248.2023.06.001

Abstract

Abstract:

Pathologically, vascular endothelial cell dysfunction leads to coagulation cascade and inflammatory processes. They are closely linked by both physical interactions and soluble factors regulation among endothelial cells, platelets, and white blood cells. Together, they constitute the process of "thromboinflammation". Thromboinflammation significantly contributes to the pathogenesis of large artery atherosclerotic ischemic stroke, acute stroke injury, and reperfusion injury, as well as stroke recurrence. Understanding the role of thromboinflammation in ischemic stroke is of great significance for the treatment and secondary prevention of the disease. This article reviews the recent research progress on the mechanism of thromboinflammation and its role in the development of ischemic stroke.

Key words: Thromboinflammation, Ischemic stroke, Atherosclerosis, Reperfusion injury

Xinya Zheng, Baoshan Qiu, Yilong Wang. Research progress on the mechanism of thromboinflammation in the occurrence and development of ischemic stroke[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(06): 533-538.

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References 45

1	规范指导临床办公室国家百万减残工程, 中国老年医学学会脑血管病分会. 远隔缺血适应防治缺血性脑血管病中国专家共识 [J]. 中华医学杂志, 2021, 101(25): 1953-1967.
2	De Meyer SF, Denorme F, Langhauser F, et al. Thromboinflammation in stroke brain damage [J]. Stroke, 2016, 47(4): 1165-1172.
3	Stoll G, Nieswandt B. Thrombo-inflammation in acute ischaemic stroke-implications for treatment [J]. Nat Rev Neurol, 2019, 15(8): 473-481.
4	Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms [J]. Blood, 2019, 133(9): 906-918.
5	Pham M, Helluy X, Kleinschnitz C, et al. Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia: an MRI study at 17.6 Tesla [J]. PLoS One, 2011, 6(4): e18386.
6	Chou ML, Babamale AO, Walker TL, et al. Blood-brain crosstalk: the roles of neutrophils, platelets, and neutrophil extracellular traps in neuropathologies [J]. Trends Neurosci, 2023, 46(9): 764-779.
7	Stuckey SM, Ong LK, Collins-Praino LE, et al. Neuroinflammation as a key driver of secondary neurodegeneration following stroke? [J]. Int J Mol Sci, 2021, 22(23): 13101.
8	Constantinescu-Bercu A, Grassi L, Frontini M, et al. Activated α(IIb)β(3) on platelets mediates flow-dependent NETosis via SLC44A2 [J]. Elife, 2020, 9: e53353.
9	Müller F, Mutch NJ, Schenk WA, et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo [J]. Cell, 2009, 139(6): 1143-1156.
10	Sonnweber T, Pizzini A, Nairz M, et al. Arachidonic acid metabolites in cardiovascular and metabolic diseases [J]. Int J Mol Sci, 2018, 19(11): 3285.
11	Darbousset R, Thomas GM, Mezouar S, et al. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation [J]. Blood, 2012, 120(10): 2133-2143.
12	Furie B, Furie BC. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation [J]. Trends Mol Med, 2004, 10(4): 171-178.
13	Asgari A, Jurasz P. Role of nitric oxide in megakaryocyte function [J]. Int J Mol Sci, 2023, 24(9): 8145.
14	Machlus KR, Johnson KE, Kulenthirarajan R, et al. CCL5 derived from platelets increases megakaryocyte proplatelet formation [J]. Blood, 2016, 127(7): 921-926.
15	Gorudko IV, Sokolov AV, Shamova EV, et al. Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry [J]. Biol Open, 2013, 2(9): 916-923.
16	Wagner DD, Heger LA. Thromboinflammation: from atherosclerosis to COVID-19 [J]. Arterioscler Thromb Vasc Biol, 2022, 42(9): 1103-1112.
17	Thiam HR, Wong SL, Wagner DD, et al. Cellular mechanisms of NETosis [J]. Annu Rev Cell Dev Biol, 2020, 36: 191-218.
18	Fuchs TA, Brill A, Duerschmied D, et al. Extracellular DNA traps promote thrombosis [J]. Proc Natl Acad Sci U S A, 2010, 107(36): 15880-15885.
19	Zhu C, Tian B. Intracranial atherosclerotic plaques identified on vessel wall imaging are associated with increased risk of first-ever stroke in a large Chinese cohort [J]. Eur J Neurol, 2023, 30(12): 3635-3636.
20	Roth S, Singh V, Tiedt S, et al. Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke [J]. Sci Transl Med, 2018, 10(432): eaao1313.
21	Zietz A, Gorey S, Kelly PJ, et al. Targeting inflammation to reduce recurrent stroke [J]. Int J Stroke, 2023: 17474930231207777.
22	Pircher J, Engelmann B, Massberg S, et al. Platelet-neutrophil crosstalk in atherothrombosis [J]. Thromb Haemost, 2019, 119(8): 1274-1282.
23	Libby P. Targeting inflammatory pathways in cardiovascular disease: the inflammasome, interleukin-1, interleukin-6 and beyond [J]. Cells, 2021, 10(4): 951.
24	Ridker PM. The time to initiate anti-inflammatory therapy for patients with chronic coronary atherosclerosis has arrived [J]. Circulation, 2023, 148(14): 1071-1073.
25	Braun LJ, Stegmeyer RI, Schäfer K, et al. Platelets docking to VWF prevent leaks during leukocyte extravasation by stimulating Tie-2 [J]. Blood, 2020, 136(5): 627-639.
26	Szepanowski RD, Haupeltshofer S, Vonhof SE, et al. Thromboinflammatory challenges in stroke pathophysiology [J]. Semin Immunopathol, 2023, 45(3): 389-410.
27	Zhang X, Gong P, Zhao Y, et al. Endothelial caveolin-1 regulates cerebral thrombo-inflammation in acute ischemia/reperfusion injury [J]. EBioMedicine, 2022, 84: 104275.
28	Cui J, Li H, Chen Z, et al. Thrombo-inflammation and immunological response in ischemic stroke: focusing on platelet-tregs interaction [J]. Front Cell Neurosci, 2022, 16: 955385.
29	Gill D, Veltkamp R. Dynamics of T cell responses after stroke [J]. Curr Opin Pharmacol, 2016, 26: 26-32.
30	Kleinschnitz C, Kraft P, Dreykluft A, et al. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature [J]. Blood, 2013, 121(4): 679-691.
31	Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology [J]. Physiol Rev, 2007, 87(1): 245-313.
32	Nieswandt B, Kleinschnitz C, Stoll G. Ischaemic stroke: a thrombo-inflammatory disease? [J]. J Physiol, 2011, 589(17): 4115-4123.
33	Santos-Lima B, Pietronigro EC, Terrabuio E, et al. The role of neutrophils in the dysfunction of central nervous system barriers [J]. Front Aging Neurosci, 2022, 14: 965169.
34	戚智锋, 罗玉敏, 刘克建. 自由基和基质金属蛋白酶介导脑缺血血脑屏障损伤的研究进展 [J]. 生物物理学报, 2012, 28(5): 383-391.
35	Stark K, Massberg S. Interplay between inflammation and thrombosis in cardiovascular pathology [J]. Nat Rev Cardiol, 2021, 18(9): 666-682.
36	Zhang Z, Shen C, Fang M, et al. Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke [J]. Cell Mol Life Sci, 2022, 79(5): 240.
37	Hernández-Jiménez M, Abad-Santos F, Cotgreave I, et al. Safety and efficacy of ApTOLL in patients with ischemic stroke undergoing endovascular treatment: a phase 1/2 randomized clinical trial [J]. JAMA Neurol, 2023, 80(8): 779-788.
38	Ramiro L, Simats A, García-Berrocoso T, et al. Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management [J]. Ther Adv Neurol Disord, 2018, 11: 1756286418789340.
39	贾建平, 陈生弟. 神经病学 [M]. 8版. 北京: 人民卫生出版社, 2021: 204-207.
40	McCabe JJ, Camps-Renom P, Giannotti N, et al. Carotid plaque inflammation imaged by PET and prediction of recurrent stroke at 5 years [J]. Neurology, 2021, 97(23): e2282-e2291.
41	Foschi M, Padroni M, Abu-Rumeileh S, et al. Diagnostic and prognostic blood biomarkers in transient ischemic attack and minor ischemic stroke: an up-to-date narrative review [J]. Stroke Cerebrovasc Dis, 2022, 31(3): 106292.
42	Yang M, Pan Y, Li Z, et al. Platelet count predicts adverse clinical outcomes after ischemic stroke or TIA: subgroup analysis of CNSR II [J]. Front Neurol, 2019, 10: 370.
43	Whiteley W, Wardlaw J, Dennis M, et al. Blood biomarkers for the diagnosis of acute cerebrovascular diseases: a prospective cohort study [J]. Cerebrovasc Dis, 2011, 32(2): 141-147.
44	Khandkar C, Vaidya K, Patel S. Colchicine for stroke prevention: a systematic review and meta-analysis [J]. Clin Ther, 2019, 41(3): 582-590.
45	Wang Y, Li J, Johnston SC, et al. Colchicine in high-risk patients with acute minor-to-moderate ischemic stroke or transient ischemic attack (CHANCE-3): rationale and design of a multicenter randomized placebo-controlled trial [J]. Int J Stroke, 2023, 18(7): 873-878.

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