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Molecular Biology

Inflammation increases MMP levels via PGE2 in human vascular wall and plasma of obese women

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Abstract

Background and objectives:

Matrix metalloproteinases (MMPs) are involved in several inflammatory processes including obesity-related vascular diseases and graft failure of coronary artery (CA) bypass grafts [internal mammary artery (IMA), saphenous vein (SV)]. In these inflammatory conditions, the release of prostaglandin E2 (PGE2) is increased via the activity of inducible microsomal PGE synthase-1 (mPGES-1). Our aim was to investigate whether MMPs and their endogenous inhibitor (TIMPs) may be regulated by PGE2 under inflammatory conditions in human vasculature and perivascular adipose tissue (PVAT), as well as in plasma of obese patients.

Methods:

MMP-1,-2 and TIMP-1,-2 densities were measured in human plasma (n = 68) as well as in supernatants of human vascular wall (IMA n = 16, SV n = 14, CA n = 13) and their PVAT. The effects of inflammation and mPGES-1 inhibitor (Compound III, 10 µM) on MMPs regulation were evaluated. The correlations between PGE2 and several parameters were calculated in plasma from patients with or without obesity.

Results:

The vascular wall and PVAT from SV exhibited the greatest MMP-1,-2 release. An increase of MMP-1,-2 and/or a decrease of TIMP-1 quantities have been detected under inflammation only in vascular wall not in PVAT. These changes under inflammation were completely reversed by inhibition of mPGES-1. In obesity, C-reactive protein (CRP), biomarker of inflammation, and PGE2 levels were increased. PGE2 contents were positively correlated with some anthropometric parameters and plasmatic CRP in both genders, while the correlation with the plasmatic MMP-1 density was significant only in women.

Conclusions:

The greater MMP activity observed in SV may contribute to the increased prevalence of graft failure. Under inflammation, the greater mPGES-1 and PGE2 levels lead to enhanced MMP activity in human vascular walls. The positive association between PGE2 and MMP-1 or CRP has been observed in plasma of women. We suggest that mPGES-1 inhibitors could prevent graft failure and obesity-related vascular remodeling mostly in women.

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References

  1. Gomez I, Foudi N, Longrois D, Norel X. The role of prostaglandin E2 in human vascular inflammation. Prostaglandins Leukot Essent Fatty Acids. 2013;89:55–63.

    Article  CAS  PubMed  Google Scholar 

  2. Bishop-Bailey D, Pepper JR, Haddad EB, Newton R, Larkin SW, Mitchell JA. Induction of cyclooxygenase-2 in human saphenous vein and internal mammary artery. Arterioscler Thromb Vasc Biol. 1997;17:1644–8.

    Article  CAS  PubMed  Google Scholar 

  3. Bishop-Bailey D, Pepper JR, Larkin SW, Mitchell JA. Differential induction of cyclooxygenase-2 in human arterial and venous smooth muscle: role of endogenous prostanoids. Arterioscler Thromb Vasc Biol. 1998;18:1655–61.

    Article  CAS  PubMed  Google Scholar 

  4. Camacho M, Gerboles E, Escudero JR, Anton R, Garcia-Moll X, Vila L. Microsomal prostaglandin E synthase-1, which is not coupled to a particular cyclooxygenase isoenzyme, is essential for prostaglandin E(2) biosynthesis in vascular smooth muscle cells. J Thromb Haemost. 2007;5:1411–9.

    Article  CAS  PubMed  Google Scholar 

  5. Camacho M, Rodriguez C, Guadall A, Alcolea S, Orriols M, Escudero JR, et al. Hypoxia upregulates PGI-synthase and increases PGI(2) release in human vascular cells exposed to inflammatory stimuli. J Lipid Res. 2011;52:720–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gomez I, Benyahia C, Louedec L, Leseche G, Jacob MP, Longrois D, et al. Decreased PGE(2) content reduces MMP-1 activity and consequently increases collagen density in human varicose vein. PLoS ONE. 2014;9:e88021.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gomez I, Ozen G, Deschildre C, Amgoud Y, Boubaya L, Gorenne I, et al. Reverse regulatory pathway (H2S / PGE2 / MMP) in human aortic aneurysm and saphenous vein varicosity. PLoS ONE. 2016;11:e0158421.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yokoyama U, Ishiwata R, Jin MH, Kato Y, Suzuki O, Jin H, et al. Inhibition of EP4 signaling attenuates aortic aneurysm formation. PLoS ONE. 2012;7:e36724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Unemori EN, Lark MW, et al. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res. 1994;75:181–9.

    Article  CAS  PubMed  Google Scholar 

  10. Montero I, Orbe J, Varo N, Beloqui O, Monreal JI, Rodriguez JA, et al. C-reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis. J Am Coll Cardiol. 2006;47:1369–78.

    Article  CAS  PubMed  Google Scholar 

  11. Qin W, Lu W, Li H, Yuan X, Li B, Zhang Q, et al. Melatonin inhibits IL1beta-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing NF-kappaB activation. J Endocrinol. 2012;214:145–53.

    Article  CAS  PubMed  Google Scholar 

  12. Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby P. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci. 1995;748:501–7.

    Article  CAS  PubMed  Google Scholar 

  13. Reuben PM, Cheung HS. Regulation of matrix metalloproteinase (MMP) gene expression by protein kinases. Front Biosci. 2006;11:1199–215.

    Article  CAS  PubMed  Google Scholar 

  14. Anstadt MP, Franga DL, Portik-Dobos V, Pennathur A, Bannan M, Mawulawde K, et al. Native matrix metalloproteinase characteristics may influence early stenosis of venous versus arterial coronary artery bypass grafting conduits. Chest. 2004;125:1853–8.

    Article  CAS  PubMed  Google Scholar 

  15. Ozen G, Topal G, Gomez I, Ghorreshi A, Boukais K, Benyahia C, et al. Control of human vascular tone by prostanoids derived from perivascular adipose tissue. Prostaglandins Other Lipid Mediat. 2013;107:13–7.

    Article  CAS  PubMed  Google Scholar 

  16. Turner NA, Ho S, Warburton P, O’Regan DJ, Porter KE. Smooth muscle cells cultured from human saphenous vein exhibit increased proliferation, invasion, and mitogen-activated protein kinase activation in vitro compared with paired internal mammary artery cells. J Vasc Surg. 2007;45:1022–8.

    Article  PubMed  Google Scholar 

  17. Ozen G, Gomez I, Daci A, Deschildre C, Boubaya L, Teskin O, et al. Inhibition of microsomal PGE synthase-1 reduces human vascular tone by increasing PGI2: a safer alternative to COX-2 inhibition. Br J Pharmacol. 2017;174:4087–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun Y, Kang L, Li J, Liu H, Wang Y, Wang C, et al. Advanced glycation end products impair the functions of saphenous vein but not thoracic artery smooth muscle cells through RAGE/MAPK signalling pathway in diabetes. J Cell Mol Med. 2016;20:1945–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ozen G, Daci A, Norel X, Topal G. Human perivascular adipose tissue dysfunction as a cause of vascular disease: focus on vascular tone and wall remodeling. Eur J Pharmacol. 2015;766:16–24.

    Article  CAS  PubMed  Google Scholar 

  20. Yun CH, Lin TY, Wu YJ, Liu CC, Kuo JY, Yeh HI, et al. Pericardial and thoracic peri-aortic adipose tissues contribute to systemic inflammation and calcified coronary atherosclerosis independent of body fat composition, anthropometric measures and traditional cardiovascular risks. Eur J Radiol. 2012;81:749–56.

    Article  PubMed  Google Scholar 

  21. Taylor LE, Sullivan JC. Sex differences in obesity-induced hypertension and vascular dysfunction: a protective role for estrogen in adipose tissue inflammation? Am J Physiol Regul Integr Comp Physiol. 2016;311:R714–20.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Xia N, Li H. The role of perivascular adipose tissue in obesity-induced vascular dysfunction. Br J Pharmacol. 2017;174:3425–42.

    Article  CAS  PubMed  Google Scholar 

  23. Rocha VZ, Libby P. Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol. 2009;6:399–409.

    Article  CAS  PubMed  Google Scholar 

  24. Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, et al. Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. J Am Coll Cardiol. 2013;62:128–35.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ketonen J, Shi J, Martonen E, Mervaala E. Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57Bl/6 mice. Circ J. 2010;74:1479–87.

    Article  CAS  PubMed  Google Scholar 

  26. Marchesi C, Ebrahimian T, Angulo O, Paradis P, Schiffrin EL. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension. 2009;54:1384–92.

    Article  CAS  PubMed  Google Scholar 

  27. Bruins P, te Velthuis H, Yazdanbakhsh AP, Jansen PG, van Hardevelt FW, de Beaumont EM, et al. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation. 1997;96:3542–8.

    Article  CAS  PubMed  Google Scholar 

  28. Faymonville ME, Deby-Dupont G, Larbuisson R, Deby C, Bodson L, Limet R, et al. Prostaglandin E2, prostacyclin, and thromboxane changes during nonpulsatile cardiopulmonary bypass in humans. J Thorac Cardiovasc Surg. 1986;91:858–66.

    CAS  PubMed  Google Scholar 

  29. Joffs C, Gunasinghe HR, Multani MM, Dorman BH, Kratz JM, Crumbley AJ 3rd, et al. Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases. Ann Thorac Surg. 2001;71:1518–23.

    Article  CAS  PubMed  Google Scholar 

  30. Sesso HD, Wang L, Buring JE, Ridker PM, Gaziano JM. Comparison of interleukin-6 and C-reactive protein for the risk of developing hypertension in women. Hypertension. 2007;49:304–10.

    Article  CAS  PubMed  Google Scholar 

  31. Ogihara T, Gotoh S, Tabuchi Y, Kumahara Y. Involvement of endogenous prostaglandins in salt-induced hypertension. Acta Endocrinol (Copenh). 1985;108:114–8.

    Article  CAS  Google Scholar 

  32. Yasmin, McEniery CM, Wallace S, Dakham Z, Pulsalkar P, Maki-Petaja K, et al. Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness. Arterioscler Thromb Vasc Biol. 2005;25:372.

    Article  CAS  PubMed  Google Scholar 

  33. Derosa G, Maffioli P, D’Angelo A, Salvadeo SA, Ferrari I, Fogari E, et al. Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in combined dyslipidemia. Clin Invest Med. 2009;32:E124–32.

    Article  CAS  PubMed  Google Scholar 

  34. Virdis A, Duranti E, Rossi C, Dell’Agnello U, Santini E, Anselmino M, et al. Tumour necrosis factor-alpha participates on the endothelin-1/nitric oxide imbalance in small arteries from obese patients: role of perivascular adipose tissue. Eur Heart J. 2015;36:784–94.

    Article  CAS  PubMed  Google Scholar 

  35. British Pharmacological Society. Contractions of human coronary vessels induced by prostaglandin E2 are mediated via EP3 receptor and modulated by perivascular adipose tissue. Pharmacology. 2015. http://www.pa2online.org/abstract/abstract.jsp?abid=32972&author=Ozen&cat=-1&period=-1.

  36. Gomez I, Benyahia C, Le Dall J, Payre C, Louedec L, Leseche G, et al. Absence of inflammatory conditions in human varicose saphenous veins. Inflamm Res. 2013;62:299–308.

    Article  CAS  PubMed  Google Scholar 

  37. Jabs WJ, Theissing E, Nitschke M, Bechtel JF, Duchrow M, Mohamed S, et al. Local generation of C-reactive protein in diseased coronary artery venous bypass grafts and normal vascular tissue. Circulation. 2003;108:1428–31.

    Article  CAS  PubMed  Google Scholar 

  38. Foudi N, Louedec L, Cachina T, Brink C, Norel X. Selective cyclooxygenase-2 inhibition directly increases human vascular reactivity to norepinephrine during acute inflammation. Cardiovasc Res. 2009;81:269–77.

    Article  CAS  PubMed  Google Scholar 

  39. Leclerc P, Idborg H, Spahiu L, Larsson C, Nekhotiaeva N, Wannberg J, et al. Characterization of a human and murine mPGES-1 inhibitor and comparison to mPGES-1 genetic deletion in mouse models of inflammation. Prostaglandins Other Lipid Mediat. 2013;107:26–34.

    Article  CAS  PubMed  Google Scholar 

  40. Kim FY, Marhefka G, Ruggiero NJ, Adams S, Whellan DJ. Saphenous vein graft disease: review of pathophysiology, prevention, and treatment. Cardiol Rev. 2013;21:101–9.

    Article  PubMed  Google Scholar 

  41. Sur S, Sugimoto JT, Agrawal DK. Coronary artery bypass graft: why is the saphenous vein prone to intimal hyperplasia? Can J Physiol Pharmacol. 2014;92:531–45.

    Article  CAS  PubMed  Google Scholar 

  42. Sukhova GK, Schonbeck U, Rabkin E, Schoen FJ, Poole AR, Billinghurst RC, et al. Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation. 1999;99:2503–9.

    Article  CAS  PubMed  Google Scholar 

  43. Moore CS, Crocker SJ. An alternate perspective on the roles of TIMPs and MMPs in pathology. Am J Pathol. 2012;180:12–6.

    Article  CAS  PubMed  Google Scholar 

  44. Dashwood MR, Tsui JC. ‘No-touch’ saphenous vein harvesting improves graft performance in patients undergoing coronary artery bypass surgery: a journey from bedside to bench. Vasc Pharmacol. 2013;58:240–50.

    Article  CAS  Google Scholar 

  45. Costa RM, Neves KB, Tostes RC, Lobato NS. Perivascular adipose tissue as a relevant fat depot for cardiovascular risk in obesity. Front Physiol. 2018;9:253.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Paz MA, Lupon J, Bosch X, Pomar JL, Sanz G. Predictors of early saphenous vein aortocoronary bypass graft occlusion. The GESIC Study Group. Ann Thorac Surg. 1993;56:1101–6.

    Article  CAS  PubMed  Google Scholar 

  47. Samuvel DJ, Jin J, Sundararaj KP, Li Y, Zhang X, Lopes-Virella MF, et al. TLR4 activation and IL-6-mediated cross talk between adipocytes and mononuclear cells synergistically stimulate MMP-1 expression. Endocrinology. 2011;152:4662–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. DeVallance E, Branyan KW, Lemaster K, Olfert IM, Smith DM, Pistilli EE et al. Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFalpha and NOX2 dependent pathway. Exp Physiol. 2018;103:590–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Moe KT, Naylynn TM, Yin NO, Khairunnisa K, Allen JC, Wong MC, et al. Tumor necrosis factor-alpha induces aortic intima-media thickening via perivascular adipose tissue inflammation. J Vasc Res. 2013;50:228–37.

    Article  CAS  PubMed  Google Scholar 

  50. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107:499–511.

    Article  Google Scholar 

  51. Garcia-Alonso V, Titos E, Alcaraz-Quiles J, Rius B, Lopategi A, Lopez-Vicario C, et al. Prostaglandin E2 exerts multiple regulatory actions on human obese adipose tissue remodeling, inflammation, adaptive thermogenesis and lipolysis. PLoS ONE. 2016;11:e0153751.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Cunha NV, de Abreu SB, Panis C, Grassiolli S, Guarnier FA, Cecchini R, et al. Cox-2 inhibition attenuates cardiovascular and inflammatory aspects in monosodium glutamate-induced obese rats. Life Sci. 2010;87:375–81.

    Article  CAS  PubMed  Google Scholar 

  53. Pham Huu C, Palhares de Miranda AL, Navarro-Delmasure C, Pham Huu Chanh A, Moutier R. Comparative study of the biosynthesis of PGE2, PGF2 alpha and TXA2 by different organs of genetically hypertensive (SHR) and obese-hypertensive (SHR-fa/fa) rats. Prostaglandins Leukot Med. 1987;26:21–32.

    Article  Google Scholar 

  54. Rocha-Rodrigues S, Rodriguez A, Goncalves IO, Moreira A, Maciel E, Santos S, et al. Impact of physical exercise on visceral adipose tissue fatty acid profile and inflammation in response to a high-fat diet regimen. Int J Biochem Cell Biol. 2017;87:114–24.

    Article  CAS  PubMed  Google Scholar 

  55. Wu D, Ren Z, Pae M, Han SN, Meydani SN. Diet-induced obesity has a differential effect on adipose tissue and macrophage inflammatory responses of young and old mice. Biofactors. 2013;39:326–33.

    Article  CAS  PubMed  Google Scholar 

  56. Luizon MR, Belo VA, Fernandes KS, Andrade VL, Tanus-Santos JE, Sandrim VC. Plasma matrix metalloproteinase-9 levels, MMP-9 gene haplotypes, and cardiovascular risk in obese subjects. Mol Biol Rep. 2016;43:463–71.

    Article  CAS  PubMed  Google Scholar 

  57. Gomez-Hernandez A, Sanchez-Galan E, Ortego M, Martin-Ventura JL, Blanco-Colio LM, Tarin-Vicente N, et al. Effect of intensive atorvastatin therapy on prostaglandin E2 levels and metalloproteinase-9 activity in the plasma of patients with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2008;102:12–8.

    Article  CAS  PubMed  Google Scholar 

  58. Cho BS, Roelofs KJ, Ford JW, Henke PK, Upchurch GR Jr. Decreased collagen and increased matrix metalloproteinase-13 in experimental abdominal aortic aneurysms in males compared with females. Surgery. 2010;147:258–67.

    Article  PubMed  Google Scholar 

  59. Sokolis DP, Iliopoulos DC. Impaired mechanics and matrix metalloproteinases/inhibitors expression in female ascending thoracic aortic aneurysms. J Mech Behav Biomed Mater. 2014;34:154–64.

    Article  CAS  PubMed  Google Scholar 

  60. Melekoglu R, Ciftci O, Eraslan S, Basak N, Celik E. The effects of body mass index on second-trimester amniotic fluid cytokine and matrix metalloproteinase levels. Gynecol Obstet Invest. 2018;83:70–5.

    Article  PubMed  Google Scholar 

  61. Papazoglou D, Papatheodorou K, Papanas N, Papadopoulos T, Gioka T, Kabouromiti G, et al. Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 levels in severely obese patients: what is the effect of weight loss? Exp Clin Endocrinol Diabetes. 2010;118:730–4.

    Article  CAS  PubMed  Google Scholar 

  62. Andrade VL, Petruceli E, Belo VA, Andrade-Fernandes CM, Caetano Russi CV, Bosco AA, et al. Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women. Clin Biochem. 2012;45:412–5.

    Article  CAS  PubMed  Google Scholar 

  63. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci USA. 2000;97:12729–34.

    Article  CAS  PubMed  Google Scholar 

  64. Pedersen SB, Kristensen K, Hermann PA, Katzenellenbogen JA, Richelsen B. Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha. Implications for the female fat distribution. J Clin Endocrinol Metab. 2004;89:1869–78.

    Article  CAS  PubMed  Google Scholar 

  65. Gallicchio L, Visvanathan K, Miller SR, Babus J, Lewis LM, Zacur H, et al. Body mass, estrogen levels, and hot flashes in midlife women. Am J Obstet Gynecol. 2005;193:1353–60.

    Article  CAS  PubMed  Google Scholar 

  66. Nilsson M, Dahlman I, Ryden M, Nordstrom EA, Gustafsson JA, Arner P, et al. Oestrogen receptor alpha gene expression levels are reduced in obese compared to normal weight females. Int J Obes (Lond). 2007;31:900–7.

    Article  CAS  Google Scholar 

  67. Claassen H, Steffen R, Hassenpflug J, Varoga D, Wruck CJ, Brandenburg LO, et al. 17beta-estradiol reduces expression of MMP-1, -3, and -13 in human primary articular chondrocytes from female patients cultured in a three dimensional alginate system. Cell Tissue Res. 2010;342:283–93.

    Article  CAS  PubMed  Google Scholar 

  68. Singer CF, Marbaix E, Kokorine I, Lemoine P, Donnez J, Eeckhout Y, et al. Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids. Proc Natl Acad Sci USA. 1997;94:10341–5.

    Article  CAS  PubMed  Google Scholar 

  69. Humphries KH, Gao M, Pu A, Lichtenstein S, Thompson CR. Significant improvement in short-term mortality in women undergoing coronary artery bypass surgery (1991 to 2004). J Am Coll Cardiol. 2007;49:1552–8.

    Article  PubMed  Google Scholar 

  70. Hassan A, Chiasson M, Buth K, Hirsch G. Women have worse long-term outcomes after coronary artery bypass grafting than men. Can J Cardiol. 2005;21:757–62.

    PubMed  Google Scholar 

  71. Woods SE, Noble G, Smith JM, Hasselfeld K. The influence of gender in patients undergoing coronary artery bypass graft surgery: an eight-year prospective hospitalized cohort study. J Am Coll Surg. 2003;196:428–34.

    Article  PubMed  Google Scholar 

  72. Vaccarino V, Abramson JL, Veledar E, Weintraub WS. Sex differences in hospital mortality after coronary artery bypass surgery: evidence for a higher mortality in younger women. Circulation. 2002;105:1176–81.

    Article  PubMed  Google Scholar 

  73. Korotkova M, Daha NA, Seddighzadeh M, Ding B, Catrina AI, Lindblad S, et al. Variants of gene for microsomal prostaglandin E2 synthase show association with disease and severe inflammation in rheumatoid arthritis. Eur J Hum Genet. 2011;19:908–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Scientific Research Project Coordination Unit of Istanbul University (Project number: BEK-2017-27545 and 44747) and INSERM (Institut National de la Santé et de la Recherche Médicale). GO is a recipient of a postgraduate fellowship (BIDEB-2214) from the Scientific and Technological Research Council of Turkey (TUBITAK). We thank the Department of Cardiac Surgery at Bichat Hospital Paris, France, for providing vascular preparations and the Biobank of INSERM U1148 for CA samples.

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Pharmacology, Istanbul University, Istanbul, 34116, Turkey

    G. Ozen & G. Topal

  2. Faculty of Medicine of Sousse, Department of Physiology and Functional Exploration, University of Sousse, UR 12ES06, Sousse, Tunisia

    S. Boumiza & K. Chahed

  3. INSERM U1148, LVTS, Eicosanoids and Vascular Pharmacology Group, CHU X. Bichat, 46 rue Huchard, Paris, 75018, France

    C. Deschildre, D. Longrois, JB. Michel, MP. Jacob & X. Norel

  4. Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Rheumatology Clinic, Karolinska University Hospital, Stockholm, SE-171 76, Sweden

    PJ. Jakobsson

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  1. G. Ozen
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PJJ is a member of the board of Gensynta Pharma AB. All other authors declare that they have no conflicts of interest.

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Ozen, G., Boumiza, S., Deschildre, C. et al. Inflammation increases MMP levels via PGE2 in human vascular wall and plasma of obese women. Int J Obes 43, 1724–1734 (2019). https://doi.org/10.1038/s41366-018-0235-6

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