Advancement in Research of Peroxisome Proliferator Activated Receptors and Formation of Abdominal Aortic Aneurysm_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WANGWen-da ,  CHENYue-xin , ZHENGYue-hong , LIYong-jun , LIUChang-wei

Department of Vascular Surgery, The Translational Medicine Center of PUMCH, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;

Corresponding author：

CHENYue-xin, Email: cyuexin2007@163.com

Keywords：

Abdominal aortic aneurysm; Peroxisome proliferator activated receptors; Macrophage; Cytokine

DOI：

10.7507/1007-9424.20160095

Video：

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Objective To summarize the current advancement of peroxisome proliferator activated receptors (PPARs) participating in formation of abdominal aortic aneurysm (AAA) and to find out the potential treatment strategy of AAA. Methods Relevant literatures about PPARs and formation of AAA were reviewed. Results AAA involved inflammation of all the layers of aorta, and the formation of AAA needed many kinds of inflammatory cells and cytokines. Many researches in vitro or in vivo had shown that PPARs could reduce the expression of inflammatory cytokines, to reduce formation of AAA. However, PPAR_γ was also confirmed to participate in the formation of AAA and the mechanism might be the transformation of macrophage from type 1 macrophage (M1) to type 2 macrophage (M2). According to the existing studies, the assumption could be that PPAR_γ can suppress the inflammatory function of M1 to reduce formation of AAA at the initiating stage, and promote formation of AAA by inducing the transform of macrophage to M2 at the late stage. Conclusion PPARs may be a potential targeting point for the prevention of AAA. More studies are needed to show the feasibility and to decide the application timing.

Citation： WANGWen-da, CHENYue-xin, ZHENGYue-hong, LIYong-jun, LIUChang-wei. Advancement in Research of Peroxisome Proliferator Activated Receptors and Formation of Abdominal Aortic Aneurysm. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(3): 360-364. doi: 10.7507/1007-9424.20160095 Copy

1.	Singh K, Bønaa KH, Jacobsen BK, et al. Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study: The Tromsø Study. Am J Epidemiol, 2001, 154(3): 236-244.
2.	王深明, 姚陈. 腹主动脉瘤血管腔内治疗的现状与进展. 中国普外基础与临床杂志, 2014, 21(6): 657-659.
3.	Liu G, Yang H. Modulation of macrophage activation and programming in immunity. J Cell Physiol, 2013, 228(3): 502-512.
4.	Kanematsu Y, Kanematsu M, Kurihara C, et al. Critical roles of macrophages in the formation of intracranial aneurysm. Stroke, 2011, 42(1): 173-178.
5.	Johnston KW, Rutherford RB, Tilson MD, et al. Suggested standards for reporting on arterial aneurysms. J Vasc Surg, 1991, 13(3): 452-458.
6.	Kniemeyer HW, Kessler T, Reber PU, et al. Treatment of ruptured abdominal aortic aneurysm, a permanent challenge or a waste of resources? Prediction of outcome using a multi-organ-dysfunction score Eur J Vasc Endovasc Surg, 2000, 19(2): 190-196.
7.	Blanchard JF, Armenian HK. Friesen PP. Risk factors for abdominal aortic aneurysm: results of a case-control study. Am J Epidemiol, 2000, 151(6): 575-583.
8.	Eagleton MJ. Inflammation in abdominal aortic aneurysms: cellular infiltrate and cytokine profiles. Vascular, 2012, 20(5): 278-283.
9.	Hwang JS, Kim HJ, Kim G, et al. PPARδ reduces abdominal aortic aneurysm formation in angiotensin Ⅱ-infused apolipoprotein E-deficient mice by regulating extracellular matrix homeostasis and inflammatory responses. Int J Cardiol, 2014, 174(1): 43-50.
10.	Galboiz Y, Shapiro S, Lahat N, et al. Modulation of monocytes matrix metalloproteinase-2, MT1-MMP and TIMP-2 by interferon-gamma and -beta: implications to multiple sclerosis. J Neuroimmunol, 2002, 131(1-2): 191-200.
11.	Krettek A, Sukhova GK, Schönbeck U, et al. Enhanced expression of CD44 variants in human atheroma and abdominal aortic aneurysm: possible role for a feedback loop in endothelial cells. Am J Pathol, 2004, 165(5): 1571-1581.
12.	Sun J, Sukhova GK, Yang M, et al. Mast cells modulate the pathoge nesis of elastase-induced abdominal aortic aneurysms in mice. J Clin Invest, 2007, 117(11): 3359-3368.
13.	Schönbeck U, Sukhova GK, Gerdes N, et al. T(H)2 predominant immune responses prevail in human abdominal aortic aneurysm. Am J Pathol, 2002, 161(2): 499-506.
14.	Shimizu K, Libby P, Mitchell RN. Local cytokine environments drive aneurysm formation in allografted aortas. Trends Cardiovasc Med, 2005, 15(4): 142-148.
15.	Shimizu K, Mitchell RN, Libby P. Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol, 2006, 26(5): 987-994.
16.	Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature, 2000, 405(6785): 421-424.
17.	Chawla A. Control of macrophage activation and function by PPARs. Circ Res, 2010, 106(10): 1559-1569.
18.	Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity, 2010, 32(5): 593-604.
19.	Golledge J, Muller J, Shephard N, et al. Association between osteo-pontin and human abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol, 2007, 27(3): 655-660.
20.	Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev, 2008, 19(5-6): 333-345.
21.	Bruemmer D, Collins AR, Noh G, et al. AngiotensinⅡ-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest, 2003, 112(9): 1318-1331.
22.	Golledge J, Cullen B, Rush C, et al. Peroxisome proliferator-activated receptor ligands reduce aortic dilatation in a mouse model of aortic aneurysm. Atherosclerosis, 2010, 210(1): 51-56.
23.	Satta J, Mennander A, Soini Y. Increased medial TUNEL-positive staining associated with apoptotic bodies is linked to smooth muscle cell diminution during evolution of abdominal aortic aneurysms. Ann Vasc Surg, 2002, 16(4): 462-466.
24.	Kim HJ, Ham SA, Kim SU, et al. Transforming growth factor-beta1 is a molecular target for the peroxisome proliferator-activated receptor delta. Circ Res, 2008, 102(2): 193-200.
25.	Moran CS, McCann M, Karan M, et al. Association of osteoprote-gerin with human abdominal aortic aneurysm progression. Circulation, 2005, 111(23): 3119-3125.
26.	Moran CS, Cullen B, Campbell JH, et al. Interaction between angio-tensinⅡ, osteoprotegerin, and peroxisome proliferator-activated receptor-gamma in abdominal aortic aneurysm. J Vasc Res, 2009, 46(3): 209-217.
27.	Zhang J, Fu M, Myles D, et al. PDGF induces osteoprotegerin expre-ssion in vascular smooth muscle cells by multiple signal pathways. FEBS Lett, 2002, 521(1-3): 180-184.
28.	Moran CS, Clancy P, Biros E, et al. Association of PPARgamma allelic variation, osteoprotegerin and abdominal aortic aneurysm. Clin Endocrinol (Oxf), 2010, 72(1): 128-132.
29.	Hamblin M, Chang L, Zhang H, et al. Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ deletion promotes abdominal aortic aneurysms. J Vasc Surg, 2010, 52(4): 984-993.
30.	Shimizu K, Shichiri M, Libby P, et al. Th2-predominant inflamma-tion and blockade of IFN-gamma signaling induce aneurysms in allografted aortas. J Clin Invest, 2004, 114(2): 300-308.
31.	Bouhlel MA, Derudas B, Rigamonti E, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab, 2007, 6(2): 137-143.
32.	Gordon S. Alternative activation of macrophages. Nat Rev Immunol, 2003, 3(1): 23-35.
33.	Porcheray F, Viaud S, Rimaniol AC, et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol, 2005, 142(3): 481-489.
34.	Standiford TJ, Keshamouni VG, Reddy RC. Peroxisome proliferator-activated receptor-gamma as a regulator of lung inflammation and repair. Proc Am Thorac Soc, 2005, 2(3): 226-231.
35.	Glass CK, Saijo K. Nuclear receptor transrepression pathways that regulate inflammation. Nat Rev Immunol, 2010, 10(5): 365-376.
36.	Zou S, Ren P, Nguyen M, et al. Notch signaling in descending thor-acic aortic aneurysm and dissection. PLoS One, 2012, 7(12): e52833.
37.	Wang YC, He F, Feng F, et al. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res, 2010, 70(12): 4840-4849.
38.	Zheng YH, Li FD, Tian C, et al. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensinⅡ-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One, 2013, 8(12): e83310.
39.	Xiong W, Zhao Y, Prall A, et al. Key roles of CD4+ T cells and IFN-gamma in the development of abdominal aortic aneurysms in a murine model. J Immunol, 2004, 172(4): 2607-2612.
40.	Xiong W, Mactaggart J, Knispel R, et al. Blocking TNF-alpha attenuates aneurysm formation in a murine model. J Immunol, 2009, 183(4): 2741-2746.
41.	Hans CP, Koenig SN, Huang N, et al. Inhibition of notch1 signaling reduces abdominal aortic aneurysm in mice by attenuating macrophage-mediated inflammation. Arterioscler Thromb Vasc Biol, 2012, 32(12): 3012-3023.

1. Singh K, Bønaa KH, Jacobsen BK, et al. Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study: The Tromsø Study. Am J Epidemiol, 2001, 154(3): 236-244.
2. 王深明, 姚陈. 腹主动脉瘤血管腔内治疗的现状与进展. 中国普外基础与临床杂志, 2014, 21(6): 657-659.
3. Liu G, Yang H. Modulation of macrophage activation and programming in immunity. J Cell Physiol, 2013, 228(3): 502-512.
4. Kanematsu Y, Kanematsu M, Kurihara C, et al. Critical roles of macrophages in the formation of intracranial aneurysm. Stroke, 2011, 42(1): 173-178.
5. Johnston KW, Rutherford RB, Tilson MD, et al. Suggested standards for reporting on arterial aneurysms. J Vasc Surg, 1991, 13(3): 452-458.
6. Kniemeyer HW, Kessler T, Reber PU, et al. Treatment of ruptured abdominal aortic aneurysm, a permanent challenge or a waste of resources? Prediction of outcome using a multi-organ-dysfunction score Eur J Vasc Endovasc Surg, 2000, 19(2): 190-196.
7. Blanchard JF, Armenian HK. Friesen PP. Risk factors for abdominal aortic aneurysm: results of a case-control study. Am J Epidemiol, 2000, 151(6): 575-583.
8. Eagleton MJ. Inflammation in abdominal aortic aneurysms: cellular infiltrate and cytokine profiles. Vascular, 2012, 20(5): 278-283.
9. Hwang JS, Kim HJ, Kim G, et al. PPARδ reduces abdominal aortic aneurysm formation in angiotensin Ⅱ-infused apolipoprotein E-deficient mice by regulating extracellular matrix homeostasis and inflammatory responses. Int J Cardiol, 2014, 174(1): 43-50.
10. Galboiz Y, Shapiro S, Lahat N, et al. Modulation of monocytes matrix metalloproteinase-2, MT1-MMP and TIMP-2 by interferon-gamma and -beta: implications to multiple sclerosis. J Neuroimmunol, 2002, 131(1-2): 191-200.
11. Krettek A, Sukhova GK, Schönbeck U, et al. Enhanced expression of CD44 variants in human atheroma and abdominal aortic aneurysm: possible role for a feedback loop in endothelial cells. Am J Pathol, 2004, 165(5): 1571-1581.
12. Sun J, Sukhova GK, Yang M, et al. Mast cells modulate the pathoge nesis of elastase-induced abdominal aortic aneurysms in mice. J Clin Invest, 2007, 117(11): 3359-3368.
13. Schönbeck U, Sukhova GK, Gerdes N, et al. T(H)2 predominant immune responses prevail in human abdominal aortic aneurysm. Am J Pathol, 2002, 161(2): 499-506.
14. Shimizu K, Libby P, Mitchell RN. Local cytokine environments drive aneurysm formation in allografted aortas. Trends Cardiovasc Med, 2005, 15(4): 142-148.
15. Shimizu K, Mitchell RN, Libby P. Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol, 2006, 26(5): 987-994.
16. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature, 2000, 405(6785): 421-424.
17. Chawla A. Control of macrophage activation and function by PPARs. Circ Res, 2010, 106(10): 1559-1569.
18. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity, 2010, 32(5): 593-604.
19. Golledge J, Muller J, Shephard N, et al. Association between osteo-pontin and human abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol, 2007, 27(3): 655-660.
20. Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev, 2008, 19(5-6): 333-345.
21. Bruemmer D, Collins AR, Noh G, et al. AngiotensinⅡ-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest, 2003, 112(9): 1318-1331.
22. Golledge J, Cullen B, Rush C, et al. Peroxisome proliferator-activated receptor ligands reduce aortic dilatation in a mouse model of aortic aneurysm. Atherosclerosis, 2010, 210(1): 51-56.
23. Satta J, Mennander A, Soini Y. Increased medial TUNEL-positive staining associated with apoptotic bodies is linked to smooth muscle cell diminution during evolution of abdominal aortic aneurysms. Ann Vasc Surg, 2002, 16(4): 462-466.
24. Kim HJ, Ham SA, Kim SU, et al. Transforming growth factor-beta1 is a molecular target for the peroxisome proliferator-activated receptor delta. Circ Res, 2008, 102(2): 193-200.
25. Moran CS, McCann M, Karan M, et al. Association of osteoprote-gerin with human abdominal aortic aneurysm progression. Circulation, 2005, 111(23): 3119-3125.
26. Moran CS, Cullen B, Campbell JH, et al. Interaction between angio-tensinⅡ, osteoprotegerin, and peroxisome proliferator-activated receptor-gamma in abdominal aortic aneurysm. J Vasc Res, 2009, 46(3): 209-217.
27. Zhang J, Fu M, Myles D, et al. PDGF induces osteoprotegerin expre-ssion in vascular smooth muscle cells by multiple signal pathways. FEBS Lett, 2002, 521(1-3): 180-184.
28. Moran CS, Clancy P, Biros E, et al. Association of PPARgamma allelic variation, osteoprotegerin and abdominal aortic aneurysm. Clin Endocrinol (Oxf), 2010, 72(1): 128-132.
29. Hamblin M, Chang L, Zhang H, et al. Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ deletion promotes abdominal aortic aneurysms. J Vasc Surg, 2010, 52(4): 984-993.
30. Shimizu K, Shichiri M, Libby P, et al. Th2-predominant inflamma-tion and blockade of IFN-gamma signaling induce aneurysms in allografted aortas. J Clin Invest, 2004, 114(2): 300-308.
31. Bouhlel MA, Derudas B, Rigamonti E, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab, 2007, 6(2): 137-143.
32. Gordon S. Alternative activation of macrophages. Nat Rev Immunol, 2003, 3(1): 23-35.
33. Porcheray F, Viaud S, Rimaniol AC, et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol, 2005, 142(3): 481-489.
34. Standiford TJ, Keshamouni VG, Reddy RC. Peroxisome proliferator-activated receptor-gamma as a regulator of lung inflammation and repair. Proc Am Thorac Soc, 2005, 2(3): 226-231.
35. Glass CK, Saijo K. Nuclear receptor transrepression pathways that regulate inflammation. Nat Rev Immunol, 2010, 10(5): 365-376.
36. Zou S, Ren P, Nguyen M, et al. Notch signaling in descending thor-acic aortic aneurysm and dissection. PLoS One, 2012, 7(12): e52833.
37. Wang YC, He F, Feng F, et al. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res, 2010, 70(12): 4840-4849.
38. Zheng YH, Li FD, Tian C, et al. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensinⅡ-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One, 2013, 8(12): e83310.
39. Xiong W, Zhao Y, Prall A, et al. Key roles of CD4+ T cells and IFN-gamma in the development of abdominal aortic aneurysms in a murine model. J Immunol, 2004, 172(4): 2607-2612.
40. Xiong W, Mactaggart J, Knispel R, et al. Blocking TNF-alpha attenuates aneurysm formation in a murine model. J Immunol, 2009, 183(4): 2741-2746.
41. Hans CP, Koenig SN, Huang N, et al. Inhibition of notch1 signaling reduces abdominal aortic aneurysm in mice by attenuating macrophage-mediated inflammation. Arterioscler Thromb Vasc Biol, 2012, 32(12): 3012-3023.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Advancement in Research of Peroxisome Proliferator Activated Receptors and Formation of Abdominal Aortic Aneurysm

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