The Journal of Thoracic and Cardiovascular Surgery
Volume 140, Issue 2 , Pages 305-312.e2 , August 2010

Effectiveness of combination of losartan potassium and doxycycline versus single-drug treatments in the secondary prevention of thoracic aortic aneurysm in Marfan syndrome

Received 29 March 2009 ,Revised 31 May 2009 ,Accepted 25 October 2009.

References 

  1. Judge DP, Dietz HC. Marfan's syndrome. Lancet. 2005;366:1965–1976
  2. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term β-adrenergic blockade in Marfan's syndrome. N Engl J Med. 1994;330:1335–1341
  3. Rios AS, Silber EN, Bavishi N, Varga P, Burton BK, Clark WA, et al. Effect of long-term β-blockade on aortic root compliance in patients with Marfan syndrome. Am Heart J. 1999;137:1057–1061
  4. Yin FC, Brin KP, Ting CT, Pyeritz RE. Arterial hemodynamic indexes in Marfan's syndrome. Circulation. 1989;79:854–862
  5. Chung AW, Yang HHC, Radomski MW, van Breemen C. Long-term doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in Marfan syndrome through the inhibition of matrix metalloproteinase-2 and -9. Circ Res. 2008;102:e73–e85
  6. Chung AW, Au Yeung K, Sandor GG, Judge DP, Dietz HC, van Breemen C. Loss of elastic fiber integrity and reduction of vascular smooth muscle contraction resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in the thoracic aortic aneurysm in Marfan syndrome. Circ Res. 2007;101:512–522
  7. Chung AW, Au Yeung K, Cortes SF, Sandor GG, Judge DP, Dietz HC, et al. Endothelial dysfunction and compromised eNOS/Akt signaling in the thoracic aorta during the progression of Marfan syndrome. Br J Pharmacol. 2007;150:1075–1083
  8. Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312:117–121
  9. Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, et al. Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome. Nat Genet. 2003;33:407–411
  10. Matt P, Habashi J, Carrel T, Cameron DE, Van Eyk JE, Dietz HC. Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan?. J Thorac Cardiovasc Surg. 2008;135:389–394
  11. Nataatmadja M, West M, West J, Summers K, Walker P, Nagata M, et al. Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm. Circulation. 2003;108;(1 Suppl):II329-34
  12. Ikonomidis JS, Jones JA, Barbour JR, Stroud RE, Clark LL, Kaplan BS, et al. Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with Marfan syndrome. Circulation. 2006;114(1 Suppl):I365–I370
  13. Jones KB, Myers L, Judge DP, Kirby PA, Dietz HC, Sponseller PD. Toward an understanding of dural ectasia: a light microscopy study in a murine model of Marfan syndrome. Spine. 2005;30:291–293
  14. Han YP, Tuan TL, Hughes M, Wu H, Garner WL. Transforming growth factor-β– and tumor necrosis factor-α–mediated induction and proteolytic activation of MMP-9 in human skin. J Biol Chem. 2001;276:22341–22350
  15. Wang M, Zhao D, Spinetti G, Zhang J, Jiang LQ, Pintus G, et al. Matrix metalloproteinase 2 activation of transforming growth factor-β1 (TGF-β1) and TGF-β1-type II receptor signaling within the aged arterial wall. Arterioscler Thromb Vasc Biol. 2006;26:1503–1509
  16. Clark-Greuel JN, Connolly JM, Sorichillo E, Narula NR, Rapoport HS, Mohler ER, et al. Transforming growth factor-β1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Ann Thorac Surg. 2007;83:946–953
  17. Karnik SK, Brooke BS, Bayes-Genis A, Sorensen L, Wythe JD, Schwartz RS, et al. A critical role for elastin signaling in vascular morphogenesis and disease. Development. 2003;130:411–423
  18. Davis EC. Smooth muscle cell to elastic lamina connections in developing mouse aorta. Role in aortic medial organization. Lab Invest. 1993;68:89–99
  19. Sakamoto H, Broekelmann T, Cheresh DA, Ramirez F, Rosenbloom J, Mecham RP. Cell-type specific recognition of RGD- and non-RGD-containing cell binding domains in fibrillin-1. J Biol Chem. 1996;271:4916–4922
  20. Chew DK, Conte MS, Khalil RA. Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular contraction. J Vasc Surg. 2004;40:1001–1010
  21. Tong XK, Hamel E. Transforming growth factor-β 1 impairs endothelin-1-mediated contraction of brain vessels by inducing mitogen-activated protein (MAP) kinase phosphatase-1 and inhibiting p38 MAP kinase. Mol Pharmacol. 2007;72:1476–1483
  22. Sharma K, Deelman L, Madesh M, Kurz B, Ciccone E, Siva S, et al. Involvement of transforming growth factor-β in regulation of calcium transients in diabetic vascular smooth muscle cells. Am J Physiol Renal Physiol. 2003;285:F1258–F1270
  23. Saura M, Zaragoza C, Cao W, Bao C, Rodríguez-Puyol M, Rodríguez-Puyol D, et al. Smad2 mediates transforming growth factor-β induction of endothelial nitric oxide synthase expression. Circ Res. 2002;91:806–813
  24. Grainger DJ, Kemp PR, Metcalfe JC, Liu AC, Lawn RM, Williams NR, et al. The serum concentration of active transforming growth factor-β is severely depressed in advanced atherosclerosis. Nat Med. 1995;1:74–79
  25. Schleicher M, Sessa WC. Are the mechanisms for NO-dependent vascular remodeling different from vasorelaxation in vivo?. Arterioscler Thromb Vasc Biol. 2008;28:1207–1208

 Supported by an operating grant from Canadian Institutes of Health Research. A.W.Y.C. is the recipient of Michael Smith Foundation for Health Research/St Paul Hospital's Foundation Trainee Award. H.H.C.Y. is the recipient of Michael Smith Foundation for Health Research Junior Trainee Award and NSERC: Alexander Graham Bell Canada Graduate Scholarship.

 Disclosures: None.

PII: S0022-5223(09)01406-8

doi: 10.1016/j.jtcvs.2009.10.039

The Journal of Thoracic and Cardiovascular Surgery
Volume 140, Issue 2 , Pages 305-312.e2 , August 2010