REFERENCES

1. Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiology of chronic venous insufficiency and varicose veins. Ann Epidemiol 2005;15:175-84.

2. Burkitt DP, Townsend AJ, Patel K, Skaug K. Varicose veins in developing countries. Lancet 1976;2:202-3.

3. Lee AJ, Evans CJ, Allan PL, Ruckley CV, Fowkes FG. Lifestyle factors and the risk of varicose veins: Edinburgh Vein Study. J Clin Epidemiol 2003;56:171-9.

4. Durham JD, Machan L. Pelvic congestion syndrome. Semin Intervent Radiol 2013;30:372-80.

5. Feldner A, Otto H, Rewerk S, Hecker M, Korff T. Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1. FASEB J 2011;25:3613-21.

6. Pfisterer L, König G, Hecker M, Korff T. Pathogenesis of varicose veins-lessons from biomechanics. Vasa 2014;43:88-99.

7. Ligi D, Croce L, Mannello F. Chronic venous disorders: the dangerous, the good, and the diverse. Int J Mol Sci 2018;19:2544.

8. Wali MA, Eid RA. Changes of elastic and collagen fibers in varicose veins. Int Angiol 2002;21:337-43.

9. Somers P, Knaapen M. The histopathology of varicose vein disease. Angiology 2006;57:546-55.

10. Sansilvestri-Morel P, Rupin A, Jaisson S, Fabiani JN, Verbeuren TJ, Vanhoutte PM. Synthesis of collagen is dysregulated in cultured fibroblasts derived from skin of subjects with varicose veins as it is in venous smooth muscle cells. Circulation 2002;106:479-83.

11. Lim CS, Davies AH. Pathogenesis of primary varicose veins. Br J Surg 2009;96:1231-42.

12. Gomez I, Benyahia C, Louedec L, et al. Decreased PGE₂ content reduces MMP-1 activity and consequently increases collagen density in human varicose vein. PLoS One 2014;9:e88021.

13. Biagi G, Lapilli A, Zendron R, Piccinni L, Coccheri S. Prostanoid production in varicose veins: evidence for decreased prostacyclin with increased thromboxane A2 and prostaglandin E2 formation. Angiology 1988;39:1036-42.

14. Bertrand-Thiebault C, Ferrari L, Boutherin-Falson O, et al. Cytochromes P450 are differently expressed in normal and varicose human saphenous veins: linkage with varicosis. Clin Exp Pharmacol Physiol 2004;31:295-301.

15. Zhao H, Hiroi T, Hansen BS, Rade JJ. Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial cells via activation of nuclear factor kappa-beta. Biochem Biophys Res Commun 2009;389:599-601.

16. Avendaño MS, Martínez-Revelles S, Aguado A, et al. Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension. Br J Pharmacol 2016;173:1541-55.

17. Pfisterer L, Meyer R, Feldner A, Drews O, Hecker M, Korff T. Bortezomib protects from varicose-like venous remodeling. FASEB J 2014;28:3518-27.

18. Eschrich J, Meyer R, Kuk H, Wagner AH, Noppeney T, Debus S, et al. Varicose remodeling of veins is suppressed by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. J Am Heart Assoc 2016;5:e002405.

19. Kuk H, Arnold C, Meyer R, Hecker M, Korff T. Magnolol inhibits venous remodeling in mice. Sci Rep 2017;7:17820.

20. Kuk H, Arnold C, Wagner AH, Hecker M, Sticht C, Korff T. Glycyrrhetinic acid antagonizes pressure-induced venous remodeling in mice. Front Physiol 2018;9:320.

21. Mitchell JA, Kirkby NS. Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system. Br J Pharmacol 2019;176:1038-50.

22. Kirkby NS, Lundberg MH, Harrington LS, et al. Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system. Proc Natl Acad Sci U S A 2012;109:17597-602.

23. Zhang J, Zou F, Tang J, et al. Cyclooxygenase-2-derived prostaglandin E₂ promotes injury-induced vascular neointimal hyperplasia through the E-prostanoid 3 receptor. Circ Res 2013;113:104-14.

24. Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM. Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem 1993;268:9049-54.

25. Baker CS, Hall RJ, Evans TJ, et al. Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arterioscler Thromb Vasc Biol 1999;19:646-55.

26. Kirkby NS, Chan MV, Zaiss AK, et al. Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-kappaB and NFAT transcriptional pathways. Proc Natl Acad Sci U S A 2016;113:434-9.

27. Nakayama T. Genetic polymorphisms of prostacyclin synthase gene and cardiovascular disease. Int Angiol 2010;29(2 Suppl):33-42.

28. Midgett C, Stitham J, Martin K, Hwa J. Prostacyclin receptor regulation--from transcription to trafficking. Curr Mol Med 2011;11:517-28.

29. Yokoyama C, Yabuki T, Shimonishi M, et al. Prostacyclin-deficient mice develop ischemic renal disorders, including nephrosclerosis and renal infarction. Circulation 2002;106:2397-403.

30. Foudi N, Gomez I, Benyahia C, Longrois D, Norel X. Prostaglandin E2 receptor subtypes in human blood and vascular cells. Eur J Pharmacol 2012;695:1-6.

31. Wang M, Ihida-Stansbury K, Kothapalli D, et al. Microsomal prostaglandin e2 synthase-1 modulates the response to vascular injury. Circulation 2011;123:631-9.

32. Patrono C, Patrignani P, García Rodríguez LA. Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical read-outs. J Clin Invest 2001;108:7-13.

33. Raju S, Knight A, Lamanilao L, Pace N, Jones T. Peripheral venous hypertension in chronic venous disease. J Vasc Surg Venous Lymphat Disord 2019;7:706-14.

34. Agus GB, de Angelis R, Mondani P, Moia R. Double-blind comparison of nimesulide and diclofenac in the treatment of superficial thrombophlebitis with telethermographic assessment. Drugs 1993;46 Suppl 1:200-3.