Research progress of macrophage polarization in the treatment of aortic dissection_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHAO Kaiwen , ZHANG Lei , ZHOU Jian ,  JING Zaiping

Department of Vascular Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, P. R. China;

Corresponding author：

JING Zaiping, Email: xueguanky@163.com

Keywords：

Macrophage polarization; aortic dissection; inflammation; review

DOI：

10.7507/1007-4848.202105066

Video：

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Aortic dissection is one of the most devastating cardiovascular diseases. One of the most important pathological features of aortic dissection is local inflammatory response, including the infiltration of inflammatory cells, extracellular matrix degradation, and smooth muscle cell phenotype switch. Macrophages which are the core of the inflammatory response play an extremely pivotal role in the progression of inflammation and tissue remodeling. Macrophages can be artificially divided into M1 and M2 types, of which the M1-type promotes inflammation while the M2-type is associated with the regression of inflammation and tissue healing. Mastering the switch of phenotypic transformation of macrophages may be of great help in inhibiting the inflammation of aortic tissue and facilitating tissue healing, as well as the treatment of aortic dissection. In this paper, we focus on the polarization of macrophages and discuss the role of macrophages in aortic dissection, the polarization pathway and the effect of related polarizing agents on the treatment of aortic dissection.

Citation： ZHAO Kaiwen, ZHANG Lei, ZHOU Jian, JING Zaiping. Research progress of macrophage polarization in the treatment of aortic dissection. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(7): 1055-1060. doi: 10.7507/1007-4848.202105066 Copy

1.	Evangelista A, Isselbacher EM, Bossone E, et al. Insights from the international registry of acute aortic dissection: A 20-year experience of collaborative clinical research. Circulation, 2018, 137(17): 1846-1860.
2.	Nienaber CA, Clough RE, Sakalihasan N, et al. Aortic dissection. Nat Rev Dis Primers, 2016, 2: 16071.
3.	朱泓樵, 李逸明, 周建, 等. 炎症反应参与主动脉夹层临床转归的研究进展. 中国普通外科杂志, 2020, 29(12): 1509-1514.
4.	Li X, Liu D, Zhao L, et al. Targeted depletion of monocyte/macrophage suppresses aortic dissection with the spatial regulation of MMP-9 in the aorta. Life Sci, 2020, 254: 116927.
5.	Peterson KR, Cottam MA, Kennedy AJ, et al. Macrophage-targeted therapeutics for metabolic disease. Trends Pharmacol Sci, 2018, 39(6): 536-546.
6.	Gordon S. Phagocytosis: An immunobiologic process. Immunity, 2016, 44(3): 463-475.
7.	Wang Y, Gao R, Li J, et al. Downregulation of hsa_circ_0074854 suppresses the migration and invasion in hepatocellular carcinoma via interacting with HuR and via suppressing exosomes-mediated macrophage M2 polarization. Int J Nanomedicine, 2021, 16: 2803-2818.
8.	Sica A, Mantovani A. Macrophage plasticity and polarization: In vivo veritas. J Clin Invest, 2012, 122(3): 787-795.
9.	Barrett TJ. Macrophages in atherosclerosis regression. Arterioscler Thromb Vasc Biol, 2020, 40(1): 20-33.
10.	Xiao T, Zhang L, Huang Y, et al. Sestrin2 increases in aortas and plasma from aortic dissection patients and alleviates angiotensinⅡ-induced smooth muscle cell apoptosis via the Nrf2 pathway. Life Sci, 2019, 218: 132-138.
11.	Rahman K, Fisher EA. Insights from pre-clinical and clinical studies on the role of innate inflammation in atherosclerosis regression. Front Cardiovasc Med, 2018, 5: 32.
12.	Wang X, Zhang H, Cao L, et al. The role of macrophages in aortic dissection. Front Physiol, 2020, 11: 54.
13.	李莉, 卓瑾, 郑玲, 等. 不同诱导极化方式对大鼠骨髓来源巨噬细胞增殖、凋亡及吞噬能力的影响. 中国组织工程研究, 2021, 25(25): 4032-4037.
14.	Gou W, Wang J, Song L, et al. Alpha-1 antitrypsin suppresses macrophage activation and promotes islet graft survival after intrahepatic islet transplantation. Am J Transplant, 2021, 21(5): 1713-1724.
15.	He Y, Pei JH, Li XQ, et al. IL-35 promotes EMT through STAT3 activation and induces MET by promoting M2 macrophage polarization in HCC. Biochem Biophys Res Commun, 2021, 559: 35-41.
16.	胡旺, 张占红, 冯浩杰, 等. 多房棘球蚴影响PPARβ、γ表达并调控巨噬细胞极化. 中国高原医学与生物学杂志, 2021, 42(1): 1-12.
17.	Kapoor N, Niu J, Saad Y, et al. Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP. J Immunol, 2015, 194(12): 6011-6023.
18.	Wang X, Li H, Chen S, et al. P300/CBP-associated factor (PCAF) attenuated M1 macrophage inflammatory responses possibly through KLF2 and KLF4. Immunol Cell Biol, 2021, 99(7): 724-736.
19.	Katsuki S, Koga JI, Matoba T, et al. Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages inhibits angiotensin Ⅱ-induced abdominal aortic aneurysm formation in apoe -/- mice. J Atheroscler Thromb, 2022, 29(1): 111-125.
20.	Hu G, Guo M, Xu J, et al. Nanoparticles targeting macrophages as potential clinical therapeutic agents against cancer and inflammation. Front Immunol, 2019, 10: 1998.
21.	Wang LX, Zhang SX, Wu HJ, et al. M2b macrophage polarization and its roles in diseases. J Leukoc Biol, 2019, 106(2): 345-358.
22.	Gong M, Zhuo X, Ma A. STAT6 upregulation promotes M2 macrophage polarization to suppress atherosclerosis. Med Sci Monit Basic Res, 2017, 23: 240-249.
23.	Adam M, Kooreman NG, Jagger A, et al. Systemic upregulation of IL-10 (interleukin-10) using a nonimmunogenic vector reduces growth and rate of dissecting abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol, 2018, 38(8): 1796-1805.
24.	Scola L, Di Maggio FM, Vaccarino L, et al. Role of TGF-β pathway polymorphisms in sporadic thoracic aortic aneurysm: Rs900 TGF-β2 is a marker of differential gender susceptibility. Mediators Inflamm, 2014, 2014: 165758.
25.	Bi C, Fu Y, Li B. Brain-derived neurotrophic factor alleviates diabetes mellitus-accelerated atherosclerosis by promoting M2 polarization of macrophages through repressing the STAT3 pathway. Cell Signal, 2020, 70: 109569.
26.	Li J, Xia N, Wen S, et al. IL (interleukin)-33 suppresses abdominal aortic aneurysm by enhancing regulatory T-cell expansion and activity. Arterioscler Thromb Vasc Biol, 2019, 39(3): 446-458.
27.	Gharib SA, McMahan RS, Eddy WE, et al. Transcriptional and functional diversity of human macrophage repolarization. J Allergy Clin Immunol, 2019, 143(4): 1536-1548.
28.	Svendsen P, Graversen JH, Etzerodt A, et al. Antibody-directed glucocorticoid targeting to CD163 in M2-type macrophages attenuates fructose-induced liver inflammatory changes. Mol Ther Methods Clin Dev, 2016, 4: 50-61.
29.	Razavi MK, Donohoe D, D'Agostino RB, et al. Adventitial drug delivery of dexamethasone to improve primary patency in the treatment of superficial femoral and popliteal artery disease: 12-month results from the DANCE clinical trial. JACC Cardiovasc Interv, 2018, 11(10): 921-931.
30.	Zhang L, Zhou J, Jing Z, et al. Glucocorticoids regulate the vascular remodeling of aortic dissection via the p38 MAPK-HSP27 pathway mediated by soluble TNF-RⅡ. EBioMedicine, 2018, 27: 247-257.
31.	Jackson DE. The unfolding tale of PECAM-1. FEBS Lett, 2003, 540(1-3): 7-14.
32.	Zhang G, Xue H, Sun D, et al. Soft apoptotic-cell-inspired nanoparticles persistently bind to macrophage membranes and promote anti-inflammatory and pro-healing effects. Acta Biomater, 2021, 131: 452-463.
33.	Andreata F, Syvannarath V, Clement M, et al. Macrophage CD31 signaling in dissecting aortic aneurysm. J Am Coll Cardiol, 2018, 72(1): 45-57.
34.	Wang Z, Brandt S, Medeiros A, et al. MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation. PLoS One, 2015, 10(2): e0115855.
35.	Yu Q, Li Q, Yang X, et al. Dexmedetomidine suppresses the development of abdominal aortic aneurysm by downregulating the mircoRNA-21/PDCD 4 axis. Int J Mol Med, 2021, 47(5): 90.
36.	Xue YL, Zhang SX, Zheng CF, et al. Long non-coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA-223 down-regulation in viral myocarditis. J Cell Mol Med, 2020, 24(21): 12341-12354.
37.	Martinez B, Peplow PV. Immunomodulators and microRNAs as neurorestorative therapy for ischemic stroke. Neural Regen Res, 2017, 12(6): 865-874.
38.	Kumar S, Boon RA, Maegdefessel L, et al. Role of noncoding RNAs in the pathogenesis of abdominal aortic aneurysm. Circ Res, 2019, 124(4): 619-630.
39.	Di Gregoli K, Mohamad Anuar NN, Bianco R, et al. MicroRNA-181b controls atherosclerosis and aneurysms through regulation of TIMP-3 and elastin. Circ Res, 2017, 120(1): 49-65.
40.	Essandoh K, Li Y, Huo J, et al. MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response. Shock, 2016, 46(2): 122-131.
41.	Ota K, Dambaeva S, Kim MW, et al. 1, 25-dihydroxy-vitamin D3 regulates NK-cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses. Eur J Immunol, 2015, 45(11): 3188-3199.
42.	Shojadoost B, Behboudi S, Villanueva AI, et al. Vitamin D3 modulates the function of chicken macrophages. Res Vet Sci, 2015, 100: 45-51.
43.	Manson JE, Bassuk SS, Cook NR, et al. Vitamin D, marine n-3 fatty acids, and primary prevention of cardiovascular disease current evidence. Circ Res, 2020, 126(1): 112-128.
44.	周敏, 郭银凤, 宋志霞, 等. 1, 25(OH)2D3通过VDR-PPARγ通路促使高糖诱导的M1型巨噬细胞向M2型转换. 中华肾脏病杂志, 2015, 31(6): 440-450.
45.	Legarth C, Grimm D, Krüger M, et al. Potential beneficial effects of vitamin d in coronary artery disease. Nutrients, 2019, 12(1): 99.
46.	Li L, Qiu X, Zhang N, et al. Crosstalk between adipocytes and M2 macrophages compensates for osteopenic phenotype in the Lrp5-deficient mice. Exp Biol Med (Maywood), 2021, 246(5): 572-583.
47.	Hui X, Gu P, Zhang J, et al. Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting M2 macrophage proliferation. Cell Metab, 2015, 22(2): 279-290.
48.	Wang G, Chen JJ, Deng WY, et al. CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway. Cell Death Dis, 2021, 12(3): 254.
49.	Hou Y, Yang D, Wang X, et al. Pseudoginsenoside-F11 promotes functional recovery after transient cerebral ischemia by regulating the microglia/macrophage polarization in rats. Int Immunopharmacol, 2021, 99: 107896.
50.	Ueba H, Shiomi M, Brines M, et al. Suppression of coronary atherosclerosis by helix B surface peptide, a nonerythropoietic, tissue-protective compound derived from erythropoietin. Mol Med, 2013, 19(1): 195-202.
51.	Cui J, Zhang F, Cao W, et al. Erythropoietin alleviates hyperglycaemia-associated inflammation by regulating macrophage polarization via the JAK2/STAT3 signalling pathway. Mol Immunol, 2018, 101: 221-228.

1. Evangelista A, Isselbacher EM, Bossone E, et al. Insights from the international registry of acute aortic dissection: A 20-year experience of collaborative clinical research. Circulation, 2018, 137(17): 1846-1860.
2. Nienaber CA, Clough RE, Sakalihasan N, et al. Aortic dissection. Nat Rev Dis Primers, 2016, 2: 16071.
3. 朱泓樵, 李逸明, 周建, 等. 炎症反应参与主动脉夹层临床转归的研究进展. 中国普通外科杂志, 2020, 29(12): 1509-1514.
4. Li X, Liu D, Zhao L, et al. Targeted depletion of monocyte/macrophage suppresses aortic dissection with the spatial regulation of MMP-9 in the aorta. Life Sci, 2020, 254: 116927.
5. Peterson KR, Cottam MA, Kennedy AJ, et al. Macrophage-targeted therapeutics for metabolic disease. Trends Pharmacol Sci, 2018, 39(6): 536-546.
6. Gordon S. Phagocytosis: An immunobiologic process. Immunity, 2016, 44(3): 463-475.
7. Wang Y, Gao R, Li J, et al. Downregulation of hsa_circ_0074854 suppresses the migration and invasion in hepatocellular carcinoma via interacting with HuR and via suppressing exosomes-mediated macrophage M2 polarization. Int J Nanomedicine, 2021, 16: 2803-2818.
8. Sica A, Mantovani A. Macrophage plasticity and polarization: In vivo veritas. J Clin Invest, 2012, 122(3): 787-795.
9. Barrett TJ. Macrophages in atherosclerosis regression. Arterioscler Thromb Vasc Biol, 2020, 40(1): 20-33.
10. Xiao T, Zhang L, Huang Y, et al. Sestrin2 increases in aortas and plasma from aortic dissection patients and alleviates angiotensinⅡ-induced smooth muscle cell apoptosis via the Nrf2 pathway. Life Sci, 2019, 218: 132-138.
11. Rahman K, Fisher EA. Insights from pre-clinical and clinical studies on the role of innate inflammation in atherosclerosis regression. Front Cardiovasc Med, 2018, 5: 32.
12. Wang X, Zhang H, Cao L, et al. The role of macrophages in aortic dissection. Front Physiol, 2020, 11: 54.
13. 李莉, 卓瑾, 郑玲, 等. 不同诱导极化方式对大鼠骨髓来源巨噬细胞增殖、凋亡及吞噬能力的影响. 中国组织工程研究, 2021, 25(25): 4032-4037.
14. Gou W, Wang J, Song L, et al. Alpha-1 antitrypsin suppresses macrophage activation and promotes islet graft survival after intrahepatic islet transplantation. Am J Transplant, 2021, 21(5): 1713-1724.
15. He Y, Pei JH, Li XQ, et al. IL-35 promotes EMT through STAT3 activation and induces MET by promoting M2 macrophage polarization in HCC. Biochem Biophys Res Commun, 2021, 559: 35-41.
16. 胡旺, 张占红, 冯浩杰, 等. 多房棘球蚴影响PPARβ、γ表达并调控巨噬细胞极化. 中国高原医学与生物学杂志, 2021, 42(1): 1-12.
17. Kapoor N, Niu J, Saad Y, et al. Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP. J Immunol, 2015, 194(12): 6011-6023.
18. Wang X, Li H, Chen S, et al. P300/CBP-associated factor (PCAF) attenuated M1 macrophage inflammatory responses possibly through KLF2 and KLF4. Immunol Cell Biol, 2021, 99(7): 724-736.
19. Katsuki S, Koga JI, Matoba T, et al. Nanoparticle-mediated delivery of pitavastatin to monocytes/macrophages inhibits angiotensin Ⅱ-induced abdominal aortic aneurysm formation in apoe -/- mice. J Atheroscler Thromb, 2022, 29(1): 111-125.
20. Hu G, Guo M, Xu J, et al. Nanoparticles targeting macrophages as potential clinical therapeutic agents against cancer and inflammation. Front Immunol, 2019, 10: 1998.
21. Wang LX, Zhang SX, Wu HJ, et al. M2b macrophage polarization and its roles in diseases. J Leukoc Biol, 2019, 106(2): 345-358.
22. Gong M, Zhuo X, Ma A. STAT6 upregulation promotes M2 macrophage polarization to suppress atherosclerosis. Med Sci Monit Basic Res, 2017, 23: 240-249.
23. Adam M, Kooreman NG, Jagger A, et al. Systemic upregulation of IL-10 (interleukin-10) using a nonimmunogenic vector reduces growth and rate of dissecting abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol, 2018, 38(8): 1796-1805.
24. Scola L, Di Maggio FM, Vaccarino L, et al. Role of TGF-β pathway polymorphisms in sporadic thoracic aortic aneurysm: Rs900 TGF-β2 is a marker of differential gender susceptibility. Mediators Inflamm, 2014, 2014: 165758.
25. Bi C, Fu Y, Li B. Brain-derived neurotrophic factor alleviates diabetes mellitus-accelerated atherosclerosis by promoting M2 polarization of macrophages through repressing the STAT3 pathway. Cell Signal, 2020, 70: 109569.
26. Li J, Xia N, Wen S, et al. IL (interleukin)-33 suppresses abdominal aortic aneurysm by enhancing regulatory T-cell expansion and activity. Arterioscler Thromb Vasc Biol, 2019, 39(3): 446-458.
27. Gharib SA, McMahan RS, Eddy WE, et al. Transcriptional and functional diversity of human macrophage repolarization. J Allergy Clin Immunol, 2019, 143(4): 1536-1548.
28. Svendsen P, Graversen JH, Etzerodt A, et al. Antibody-directed glucocorticoid targeting to CD163 in M2-type macrophages attenuates fructose-induced liver inflammatory changes. Mol Ther Methods Clin Dev, 2016, 4: 50-61.
29. Razavi MK, Donohoe D, D'Agostino RB, et al. Adventitial drug delivery of dexamethasone to improve primary patency in the treatment of superficial femoral and popliteal artery disease: 12-month results from the DANCE clinical trial. JACC Cardiovasc Interv, 2018, 11(10): 921-931.
30. Zhang L, Zhou J, Jing Z, et al. Glucocorticoids regulate the vascular remodeling of aortic dissection via the p38 MAPK-HSP27 pathway mediated by soluble TNF-RⅡ. EBioMedicine, 2018, 27: 247-257.
31. Jackson DE. The unfolding tale of PECAM-1. FEBS Lett, 2003, 540(1-3): 7-14.
32. Zhang G, Xue H, Sun D, et al. Soft apoptotic-cell-inspired nanoparticles persistently bind to macrophage membranes and promote anti-inflammatory and pro-healing effects. Acta Biomater, 2021, 131: 452-463.
33. Andreata F, Syvannarath V, Clement M, et al. Macrophage CD31 signaling in dissecting aortic aneurysm. J Am Coll Cardiol, 2018, 72(1): 45-57.
34. Wang Z, Brandt S, Medeiros A, et al. MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation. PLoS One, 2015, 10(2): e0115855.
35. Yu Q, Li Q, Yang X, et al. Dexmedetomidine suppresses the development of abdominal aortic aneurysm by downregulating the mircoRNA-21/PDCD 4 axis. Int J Mol Med, 2021, 47(5): 90.
36. Xue YL, Zhang SX, Zheng CF, et al. Long non-coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA-223 down-regulation in viral myocarditis. J Cell Mol Med, 2020, 24(21): 12341-12354.
37. Martinez B, Peplow PV. Immunomodulators and microRNAs as neurorestorative therapy for ischemic stroke. Neural Regen Res, 2017, 12(6): 865-874.
38. Kumar S, Boon RA, Maegdefessel L, et al. Role of noncoding RNAs in the pathogenesis of abdominal aortic aneurysm. Circ Res, 2019, 124(4): 619-630.
39. Di Gregoli K, Mohamad Anuar NN, Bianco R, et al. MicroRNA-181b controls atherosclerosis and aneurysms through regulation of TIMP-3 and elastin. Circ Res, 2017, 120(1): 49-65.
40. Essandoh K, Li Y, Huo J, et al. MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response. Shock, 2016, 46(2): 122-131.
41. Ota K, Dambaeva S, Kim MW, et al. 1, 25-dihydroxy-vitamin D3 regulates NK-cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses. Eur J Immunol, 2015, 45(11): 3188-3199.
42. Shojadoost B, Behboudi S, Villanueva AI, et al. Vitamin D3 modulates the function of chicken macrophages. Res Vet Sci, 2015, 100: 45-51.
43. Manson JE, Bassuk SS, Cook NR, et al. Vitamin D, marine n-3 fatty acids, and primary prevention of cardiovascular disease current evidence. Circ Res, 2020, 126(1): 112-128.
44. 周敏, 郭银凤, 宋志霞, 等. 1, 25(OH)2D3通过VDR-PPARγ通路促使高糖诱导的M1型巨噬细胞向M2型转换. 中华肾脏病杂志, 2015, 31(6): 440-450.
45. Legarth C, Grimm D, Krüger M, et al. Potential beneficial effects of vitamin d in coronary artery disease. Nutrients, 2019, 12(1): 99.
46. Li L, Qiu X, Zhang N, et al. Crosstalk between adipocytes and M2 macrophages compensates for osteopenic phenotype in the Lrp5-deficient mice. Exp Biol Med (Maywood), 2021, 246(5): 572-583.
47. Hui X, Gu P, Zhang J, et al. Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting M2 macrophage proliferation. Cell Metab, 2015, 22(2): 279-290.
48. Wang G, Chen JJ, Deng WY, et al. CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway. Cell Death Dis, 2021, 12(3): 254.
49. Hou Y, Yang D, Wang X, et al. Pseudoginsenoside-F11 promotes functional recovery after transient cerebral ischemia by regulating the microglia/macrophage polarization in rats. Int Immunopharmacol, 2021, 99: 107896.
50. Ueba H, Shiomi M, Brines M, et al. Suppression of coronary atherosclerosis by helix B surface peptide, a nonerythropoietic, tissue-protective compound derived from erythropoietin. Mol Med, 2013, 19(1): 195-202.
51. Cui J, Zhang F, Cao W, et al. Erythropoietin alleviates hyperglycaemia-associated inflammation by regulating macrophage polarization via the JAK2/STAT3 signalling pathway. Mol Immunol, 2018, 101: 221-228.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress of macrophage polarization in the treatment of aortic dissection

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