Pathogenesis of varicose veins

Journal of Vascular and Interventional Radiology

Volumn 23, Issue 1, 2012, Pages 33-39

  Oklu, Rahmi ^a   Habito, Roy ^a   Mayr, Manuel ^c   Deipolyi, Amy R ^a   Albadawi, Hassan ^a   Hesketh, Robin ^b   Walker, T Gregory ^a   Linskey, Katy R ^a   Long, Chandler A ^a   Wicky, Stephan ^a   Stoughton, Julianne ^a   Watkins, Michael T ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

COLLAGEN TYPE 1; COLLAGEN TYPE 3; COLLAGENASE 3; ELASTIN; FIBRILLIN; GELATINASE A; GELATINASE B; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERSTITIAL COLLAGENASE; MITOGEN ACTIVATED PROTEIN KINASE; NOTCH3 RECEPTOR; SMAD PROTEIN; TRANSCRIPTION FACTOR FOXC2; TRANSFORMING GROWTH FACTOR BETA1;

ADVENTITIA; CADASIL; CELL PROLIFERATION; CHRONIC VEIN INSUFFICIENCY; COLLAGEN SYNTHESIS; DOPPLER FLOWMETRY; ENZYME ACTIVATION; EXTRACELLULAR MATRIX; FIBROBLAST; GENE EXPRESSION; GENE MUTATION; GENETIC ANALYSIS; GENOTYPE; HUMAN; INTIMA; MICROARRAY ANALYSIS; NORRIE DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEOMICS; REVIEW; SAPHENOUS VEIN; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; TUNICA MEDIA; VARICOSIS; VASA VASORUM; VEIN WALL; VENOUS PRESSURE;

BIOLOGICAL MARKERS; GENETIC PREDISPOSITION TO DISEASE; GENOMICS; HUMANS; MUSCLE, SMOOTH, VASCULAR; RISK FACTORS; TRANSFORMING GROWTH FACTOR BETA; VARICOSE VEINS;

EID: 84855350474     PISSN: 10510443     EISSN: 15357732     Source Type: Journal    
DOI: 10.1016/j.jvir.2011.09.010     Document Type: Review

References (76)

1. Raffetto JD, Khalil RA. Mechanisms of varicose vein formation: valve dysfunction and wall dilation. Phlebology 2008; 23:85-98.
2. Bergan JJ, Schmid-Schonbein GW, Smith PD, et al. Chronic venous disease. N Engl J Med 2006; 355:488-498. (Pubitemid 44162276)
3. Meissner MH, Gloviczki P, Bergan J, et al. Primary chronic venous disorders. J Vasc Surg 2007; 46(suppl S):54S-67S.
4. Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiology of chronic venous insufficiency and varicose veins. Ann Epidemiol 2005; 15:175-184. (Pubitemid 40269465)
5. Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health 1999; 53:149-153. (Pubitemid 29086297)
6. Fowkes FG, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous insufficiency. Angiology 2001; 52(suppl 1):S5-S15. (Pubitemid 32777511)
7. Heit JA, Rooke TW, Silverstein MD, et al. Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study. J Vasc Surg 2001; 33:1022-1027. (Pubitemid 33586346)
8. Ruckley CV, Evans CJ, Allan PL, Lee AJ, Fowkes FG. Chronic venous insufficiency: clinical and duplex correlations. The Edinburgh Vein Study of venous disorders in the general population. J Vasc Surg 2002; 36:520-525.
9. Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of varicose veins: the Framingham Study. Am J Prev Med 1988; 4:96-101.
10. Hume M. Venous ulcers, the vascular surgeon, and the Medicare budget. J Vasc Surg 1992; 16:671-673.
11. Hume M. A venous renaissance? J Vasc Surg 1992; 15:947-951.
12. Patel NP, Labropoulos N, Pappas PJ. Current management of venous ulceration. Plast Reconstr Surg 2006; 117(suppl):254S-260S. (Pubitemid 44317789)
13. Labropoulos N, Giannoukas AD, Delis K, et al. Where does venous reflux start? J Vasc Surg 1997; 26:736-742. (Pubitemid 27505608)
14. Naoum JJ, Hunter GC, Woodside KJ, Chen C. Current advances in the pathogenesis of varicose veins. J Surg Res 2007; 141:311-316. (Pubitemid 47042045)
15. Rosai J, Ackerman LV. Ackerman's surgical pathology, 8th ed. St. Louis: Mosby, 1996.
16. Elsharawy MA, Naim MM, Abdelmaguid EM, Al-Mulhim AA. Role of saphenous vein wall in the pathogenesis of primary varicose veins. Interact Cardiovasc Thorac Surg 2007; 6:219-224. (Pubitemid 46596953)
17. Young B, Heath JW, Burkitt HG. Wheater's functional histology: a text and colour atlas, 4th ed. New York: Churchill Livingstone, 2000.
18. Wali MA, Dewan M, Eid RA. Histopathological changes in the wall of varicose veins. Int Angiol 2003; 22:188-193. (Pubitemid 36869390)
19. Travers JP, Brookes CE, Evans J, et al. Assessment of wall structure and composition of varicose veins with reference to collagen, elastin and smooth muscle content. Eur J Vasc Endovasc Surg 1996; 11:230-237. (Pubitemid 26120481)
20. Lim CS, Davies AH. Pathogenesis of primary varicose veins. Br J Surg 2009; 96:1231-1242.
21. Bujan J, Gimeno MJ, Jimenez JA, et al. Expression of elastic components in healthy and varicose veins. World J Surg 2003; 27:901-905. (Pubitemid 37051939)
22. Schwartz E, Fleischmajer R. Association of elastin with oxytalan fibers of the dermis and with extracellular microfibrils of cultured skin fibroblasts. J Histochem Cytochem 1986; 34:1063-1068. (Pubitemid 16058101)
23. Mecham RP, Heuser, JE. The elastic fibre. In: Hay ED, ed. Cell biology of the extracellular matrix. New York: Plenum Press, 1991;79-109.
24. Trendelenburg F. Ueber die unterbindung der vena saphena magna bei unterschenkelvaricen. Beitr Z Klin Chir 1891; 7:195-520.
25. Alexander CJ. The theoretical basis of varicose vein formation. Med J Aust 1972; 1:258-261.
26. Cotton LT. Varicose veins. Gross anatomy and development. Br J Surg 1961; 48:589-598.
27. Clarke GH, Vasdekis SN, Hobbs JT, Nicolaides AN. Venous wall function in the pathogenesis of varicose veins. Surgery 1992; 111:402-408.
28. Leu HJ, Vogt M, Pfrunder H. Morphological alterations of non-varicose and varicose veins. (A morphological contribution to the discussion on pathogenesis of varicose veins). Basic Res Cardiol 1979; 74:435-444. (Pubitemid 9244730)
29. Vanhoutte PM, Corcaud S, de Montrion C. Venous disease: from pathophysiology to quality of life. Angiology 1997; 48:559-567. (Pubitemid 27342626)
30. Woodside KJ, Hu M, Burke A, et al. Morphologic characteristics of varicose veins: possible role of metalloproteinases. J Vasc Surg 2003; 38:162-169. (Pubitemid 41123304)
31. Badier-Commander C, Verbeuren T, Lebard C, Michel JB, Jacob MP. Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation. J Pathol 2000; 192:105-112.
32. Kockx MM, Knaapen MW, Bortier HE, et al. Vascular remodeling in varicose veins. Angiology 1998; 49:871-877. (Pubitemid 28520748)
33. Sansilvestri-Morel P, Nonotte I, Fournet-Bourguignon MP, et al. Abnormal deposition of extracellular matrix proteins by cultured smooth muscle cells from human varicose veins. J Vasc Res 1998; 35:115-123. (Pubitemid 28191778)
34. Travers JP, Brookes CE, Evans J, et al. Assessment of wall structure and composition of varicose veins with reference to collagen, elastin and smooth muscle content. Eur J Vasc Endovasc Surg 1996; 11:230-237. (Pubitemid 26120481)
35. Gillespie DL, Patel A, Fileta B, et al. Varicose veins possess greater quantities of MMP-1 than normal veins and demonstrate regional variation in MMP-1 and MMP-13. J Surg Res 2002; 106:233-238.
36. Venturi M, Bonavina L, Annoni F, et al. Biochemical assay of collagen and elastin in the normal and varicose vein wall. J Surg Res 1996; 60:245-248. (Pubitemid 26044325)
37. Eklof B, Rutherford RB, Bergan JJ, et al. Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg 2004; 40:1248-1252. (Pubitemid 40037299)
38. Gandhi RH, Irizarry E, Nackman GB, et al. Analysis of the connective tissue matrix and proteolytic activity of primary varicose veins. J Vasc Surg 1993; 18:814-820. (Pubitemid 23346905)
39. Bergan JJ, Pascarella L, Schmid-Schonbein GW. Pathogenesis of primary chronic venous disease: insights from animal models of venous hypertension. J Vasc Surg 2008; 47:183-192.
40. Michiels C, Arnould T, Thibaut-Vercruyssen R, et al. Perfused human saphenous veins for the study of the origin of varicose veins: role of the endothelium and of hypoxia. Int Angiol 1997; 16:134-141. (Pubitemid 27353146)
41. Oklu R, Hesketh R. The latent transforming growth factor beta binding protein (LTBP) family. Biochem J 2000; 352:601-610. (Pubitemid 32015012)
42. Pascual G, Mendieta C, Garcia-Honduvilla N, et al. TGF-beta1 upregulation in the aging varicose vein. J Vasc Res 2007; 44:192-201. (Pubitemid 46597301)
43. Oklu R, Hesketh TR, Metcalfe JC, Kemp PR. Expression of alternatively spliced human latent transforming growth factor beta binding protein-1. FEBS Lett 1998; 435:143-148. (Pubitemid 28434988)
44. Oklu R, Metcalfe JC, Hesketh TR, Kemp PR. Loss of a consensus heparin binding site by alternative splicing of latent transforming growth factor-beta binding protein-1. FEBS Lett 1998; 425:281-285. (Pubitemid 28178908)
45. Kanzaki T, Olofsson A, Moren A, et al. TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Cell 1990; 61:1051-1061.
46. Taipale J, Lohi J, Saarinen J, Kovanen PT, Keski-Oja J. Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells. J Biol Chem 1995; 270:4689-4696.
47. Sayer GL, Smith PD. Immunocytochemical characterisation of the inflammatory cell infiltrate of varicose veins. Eur J Vasc Endovasc Surg 2004; 28:479-483. (Pubitemid 39307439)
48. Yamada T, Tomita S, Mori M, et al. Increased mast cell infiltration in varicose veins of the lower limbs: a possible role in the development of varices. Surgery 1996; 119:494-497. (Pubitemid 26141023)
49. Lal BK, Saito S, Pappas PJ, et al. Altered proliferative responses of dermal fibroblasts to TGF-beta1 may contribute to chronic venous stasis ulcer. J Vasc Surg 2003; 37:1285-1293.
50. Powell DW, Mifflin RC, Valentich JD, et al. Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 1999; 277:C1-C9.
51. Pappas PJ, Lal BK, Ohara N, et al. Regulation of matrix contraction in chronic venous disease. Eur J Vasc Endovasc Surg 2009; 38:518-529.
52. Saito S, Trovato MJ, You R, et al. Role of matrix metalloproteinases 1, 2, and 9 and tissue inhibitor of matrix metalloproteinase-1 in chronic venous insufficiency. J Vasc Surg 2001; 34:930-938. (Pubitemid 33661046)
53. Lim CS, Shalhoub J, Gohel MS, Shepherd AC, Davies AH. Matrix metalloproteinases in vascular disease--a potential therapeutic target? Curr Vasc Pharmacol 2010; 8:75-85.
54. Jacob T, Hingorani A, Ascher E. Overexpression of transforming growth factor-beta1 correlates with increased synthesis of nitric oxide synthase in varicose veins. J Vasc Surg 2005; 41:523-530. (Pubitemid 40523598)
55. Kowalewski R, Malkowski A, Sobolewski K, Gacko M. Evaluation of transforming growth factor-beta signaling pathway in the wall of normal and varicose veins. Pathobiology 2010; 77:1-6.
56. Oklu R, Walker TG, Wicky S, Hesketh R. Angiogenesis and current antiangiogenic strategies for the treatment of cancer. J Vasc Interv Radiol 2010; 21:1791-1805.
57. McCollum PT, Bush JA, James G, et al. Randomized phase II clinical trial of Avotermin versus placebo for scar improvement. Br J Surg 2011; 98:925-934.
58. Hauge M, Gundersen J. Genetics of varicose veins of the lower extremities. Hum Hered 1969; 19:573-580.
59. Matousek V, Prerovsky I. A contribution to the problem of the inheritance of primary varicose veins. Hum Hered 1974; 24:225-235.
60. Brice G, Mansour S, Bell R, et al. Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24.J Med Genet 2002; 39:478-483. (Pubitemid 34787740)
61. Ng MY, Andrew T, Spector TD, Jeffery S. Linkage to the FOXC2 region of chromosome 16 for varicose veins in otherwise healthy, unselected sibling pairs. J Med Genet 2005; 42:235-239. (Pubitemid 40380304)
62. Mellor RH, Brice G, Stanton AW, et al. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation 2007; 115:1912-1920. (Pubitemid 46598905)
63. Saiki S, Sakai K, Saiki M, et al. Varicose veins associated with CADASIL result from a novel mutation in the Notch3 gene. Neurology 2006; 67:337-339. (Pubitemid 44305431)
64. Le Flem L, Mennen L, Aubry ML, et al. Thrombomodulin promoter mutations, venous thrombosis, and varicose veins. Arterioscler Thromb Vasc Biol 2001; 21:445-451. (Pubitemid 32199129)
65. Rehm HL, Gutierrez-Espeleta GA, Garcia R, et al. Norrie disease gene mutation in a large Costa Rican kindred with a novel phenotype including venous insufficiency. Hum Mutat 1997; 9:402-408. (Pubitemid 27194892)
66. Law C, Bunyan D, Castle B, et al. Clinical features in a family with an R460H mutation in transforming growth factor beta receptor 2 gene. J Med Genet 2006; 43:908-916. (Pubitemid 46080187)
67. The Jackson Laboratory. Available at: http://www.jax.org; Accessed April 15, 2011.
68. Mayr M, Madhu B, Xu Q. Proteomics and metabolomics combined in cardiovascular research. Trends Cardiovasc Med 2007; 17:43-48. (Pubitemid 46205325)
69. Mayr M, May D, Gordon O, et al. Metabolic homeostasis is maintained in myocardial hibernation by adaptive changes in the transcriptome and proteome. J Mol Cell Cardiol 2011; 50:982-990.
70. Cario-Toumaniantz C, Boularan C, Schurgers LJ, et al. Identification of differentially expressed genes in human varicose veins: involvement of matrix Gla protein in extracellular matrix remodeling. J Vasc Res 2007; 44:444-459. (Pubitemid 350022327)
71. Mayr M, Zhang J, Greene AS, et al. Proteomics-based development of biomarkers in cardiovascular disease: mechanistic, clinical, and therapeutic insights. Mol Cell Proteomics 2006; 5:1853-1864. (Pubitemid 44688194)
72. Didangelos A, Yin X, Mandal K, et al. Proteomics characterization of extracellular space components in the human aorta. Mol Cell Proteomics 2010; 9:2048-2062.
73. Didangelos A, Simper D, Monaco C, Mayr M. Proteomics of acute coronary syndromes. Curr Atheroscler Rep 2009; 11:188-195.
74. Takase S, Lerond L, Bergan JJ, Schmid-Schonbein GW. The inflammatory reaction during venous hypertension in the rat. Microcirculation 2000; 7:41-52.
75. Takase S, Lerond L, Bergan JJ, Schmid-Schonbein GW. Enhancement of reperfusion injury by elevation of microvascular pressures. Am J Physiol Heart Circ Physiol 2002; 282:H1387-H1394. (Pubitemid 34654892)
76. Qui Y, Quijano RC, Wang SK, Hwang NH. Fluid dynamics of venous valve closure. Ann Biomed Eng 1995; 23:750-759.