The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy

Abstract

Traditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV.

Keywords

bicuspid aortic valve - aortopathy - biomarkers

• References

• 1 Basso C, Boschello M, Perrone C. , et al. An echocardiographic survey of primary school children for bicuspid aortic valve. Am J Cardiol 2004; 93 (05) 661-663
• 2 Nistri S, Basso C, Marzari C, Mormino P, Thiene G. Frequency of bicuspid aortic valve in young male conscripts by echocardiogram. Am J Cardiol 2005; 96 (05) 718-721
• 3 Panayotova R, Macnab A, Waterworth PD. A pilot project of familial screening in patients with bicuspid aortic valve disease. J Heart Valve Dis 2013; 22 (02) 150-155
• 4 Tutar E, Ekici F, Atalay S, Nacar N. The prevalence of bicuspid aortic valve in newborns by echocardiographic screening. Am Heart J 2005; 150 (03) 513-515
• 5 Fedak PWM, Verma S, David TE, Leask RL, Weisel RD, Butany J. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation 2002; 106 (08) 900-904
• 6 Girdauskas E, Borger MA, Secknus M-A, Girdauskas G, Kuntze T. Is aortopathy in bicuspid aortic valve disease a congenital defect or a result of abnormal hemodynamics? A critical reappraisal of a one-sided argument. Eur J Cardiothorac Surg 2011; 39 (06) 809-814
• 7 Hiratzka LF, Bakris GL, Beckman JA. , et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation 2010; 121 (13) e266-e369
• 8 Erbel R, Aboyans V, Boileau C. , et al; ESC Committee for Practice Guidelines; The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. Eur Heart J 2014; 35 (41) 2873-2926
• 9 Svensson LG, Adams DH, Bonow RO. , et al. Aortic valve and ascending aorta guidelines for management and quality measures. Ann Thorac Surg 2013; 95 (6, Suppl): S1-S66
• 10 von Kodolitsch Y, Robinson P, Berger J. When should surgery be performed in Marfan syndrome and other connective tissue disorders to protect against type a dissection?. In: Bonser RS, Pagano D, Haverich A, Mascaro J. eds. Controversies in Aortic Dissection and Aneurysmal Disease. London: Springer; 2014: 17-47
• 11 Charitos EI, Stierle U, Petersen M. , et al. The fate of the bicuspid valve aortopathy after aortic valve replacement. Eur J Cardiothorac Surg 2014; 45 (05) e128-e135
• 12 Itagaki S, Chikwe JP, Chiang YP, Egorova NN, Adams DH. Long-term risk for aortic complications after aortic valve replacement in patients with bicuspid aortic valve versus Marfan syndrome. J Am Coll Cardiol 2015; 65 (22) 2363-2369
• 13 Pape LA, Tsai TT, Isselbacher EM. , et al; International Registry of Acute Aortic Dissection (IRAD) Investigators. Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2007; 116 (10) 1120-1127
• 14 von Kodolitsch Y, Rybczynski M, Bernhardt A. , et al. Marfan syndrome and the evolving spectrum of heritable thoracic aortic disease: do we need genetics for clinical decisions?. Vasa 2010; 39 (01) 17-32
• 15 Borger MA, Preston M, Ivanov J. , et al. Should the ascending aorta be replaced more frequently in patients with bicuspid aortic valve disease?. J Thorac Cardiovasc Surg 2004; 128 (05) 677-683
• 16 Della Corte A, Bancone C, Dialetto G. , et al. The ascending aorta with bicuspid aortic valve: a phenotypic classification with potential prognostic significance. Eur J Cardiothorac Surg 2014; 46 (02) 240-247 , discussion 247
• 17 Nistri S, Grande-Allen J, Noale M. , et al. Aortic elasticity and size in bicuspid aortic valve syndrome. Eur Heart J 2008; 29 (04) 472-479
• 18 Rylski B, Branchetti E, Bavaria JE. , et al. Modeling of predissection aortic size in acute type A dissection: more than 90% fail to meet the guidelines for elective ascending replacement. J Thorac Cardiovasc Surg 2014; 148 (03) 944-8.e1
• 19 Girdauskas E, Rouman M, Disha K. , et al. Aortic dissection after previous aortic valve replacement for bicuspid aortic valve disease. J Am Coll Cardiol 2015; 66 (12) 1409-1411
• 20 Della Corte A, Bancone C, Quarto C. , et al. Predictors of ascending aortic dilatation with bicuspid aortic valve: a wide spectrum of disease expression. Eur J Cardiothorac Surg 2007; 31 (03) 397-404 , discussion 404–405
• 21 Fazel SS, Mallidi HR, Lee RS. , et al. The aortopathy of bicuspid aortic valve disease has distinctive patterns and usually involves the transverse aortic arch. J Thorac Cardiovasc Surg 2008; 135 (04) 901-907 , 907.e1–907.e2
• 22 Schaefer BM, Lewin MB, Stout KK. , et al. The bicuspid aortic valve: an integrated phenotypic classification of leaflet morphology and aortic root shape. Heart 2008; 94 (12) 1634-1638
• 23 Park CB, Greason KL, Suri RM, Michelena HI, Schaff HV, Sundt III TM. Fate of nonreplaced sinuses of Valsalva in bicuspid aortic valve disease. J Thorac Cardiovasc Surg 2011; 142 (02) 278-284
• 24 Mortensen K, Aydin MA, Rybczynski M. , et al. Augmentation index relates to progression of aortic disease in adults with Marfan syndrome. Am J Hypertens 2009; 22 (09) 971-979
• 25 Shim CY, Cho IJ, Yang WI. , et al. Central aortic stiffness and its association with ascending aorta dilation in subjects with a bicuspid aortic valve. J Am Soc Echocardiogr 2011; 24 (08) 847-852
• 26 Aydin A, Desai N, Bernhardt AM. , et al. Ascending aortic aneurysm and aortic valve dysfunction in bicuspid aortic valve disease. Int J Cardiol 2013; 164 (03) 301-305
• 27 Keane MG, Wiegers SE, Plappert T, Pochettino A, Bavaria JE, Sutton MG. Bicuspid aortic valves are associated with aortic dilatation out of proportion to coexistent valvular lesions. Circulation 2000; 102 (19) (Suppl. 03) III35-III39
• 28 Hillebrand M, Koschyk D, ter Hark P. , et al. Sensitivity and specificity of routine echocardiography for bicuspid aortic valve disease: Retrospective study, systematic review and meta-analysis. in preparation
• 29 Nejatian A, Yu J, Geva T, White MT, Prakash A. Aortic measurements in patients with aortopathy are larger and more reproducible by cardiac magnetic resonance compared with echocardiography. Pediatr Cardiol 2015; 36 (08) 1761-1773
• 30 Flachskampf FA, Badano L, Daniel WG. , et al; European Association of Echocardiography; Echo Committee of the European Association of Cardiothoracic Anaesthesiologists. Recommendations for transoesophageal echocardiography: update 2010. Eur J Echocardiogr 2010; 11 (07) 557-576
• 31 Suzuki T, Bossone E, Sawaki D. , et al. Biomarkers of aortic diseases. Am Heart J 2013; 165 (01) 15-25
• 32 Trimarchi S, Sangiorgi G, Sang X. , et al. In search of blood tests for thoracic aortic diseases. Ann Thorac Surg 2010; 90 (05) 1735-1742
• 33 Branchetti E, Bavaria JE, Grau JB. , et al. Circulating soluble receptor for advanced glycation end product identifies patients with bicuspid aortic valve and associated aortopathies. Arterioscler Thromb Vasc Biol 2014; 34 (10) 2349-2357
• 34 Drapisz S, Góralczyk T, Jamka-Miszalski T, Olszowska M, Undas A. Nonstenotic bicuspid aortic valve is associated with elevated plasma asymmetric dimethylarginine. J Cardiovasc Med (Hagerstown) 2013; 14 (06) 446-452
• 35 Ikonomidis JS, Ivey CR, Wheeler JB. , et al. Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease. J Thorac Cardiovasc Surg 2013; 145 (05) 1326-1333
• 36 Black KM, Masuzawa A, Hagberg RC. , et al. Preliminary biomarkers for identification of human ascending thoracic aortic aneurysm. J Am Heart Assoc 2013; 2 (06) e000138
• 37 Grewal N, Gittenberger-de Groot AC, DeRuiter MC. , et al. Bicuspid aortic valve: phosphorylation of c-Kit and downstream targets are prognostic for future aortopathy. Eur J Cardiothorac Surg 2014; 46 (05) 831-839
• 38 Apte SS, Parks WC. Metalloproteinases: a parade of functions in matrix biology and an outlook for the future. Matrix Biol 2015; 44–46: 1-6
• 39 Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 2002; 110 (05) 625-632
• 40 McMillan WD, Pearce WH. Increased plasma levels of metalloproteinase-9 are associated with abdominal aortic aneurysms. J Vasc Surg 1999; 29 (01) 122-127 , discussion 127–129
• 41 Monaco M, Stassano P, Di Tommaso L, Iannelli G. Response of plasma matrix metalloproteinases and tissue inhibitor of metalloproteinases to stent-graft surgery for descending thoracic aortic aneurysms. J Thorac Cardiovasc Surg 2007; 134 (04) 925-931
• 42 Koullias GJ, Ravichandran P, Korkolis DP, Rimm DL, Elefteriades JA. Increased tissue microarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections. Ann Thorac Surg 2004; 78 (06) 2106-2110 , discussion 2110–2111
• 43 Schmoker JD, McPartland KJ, Fellinger EK. , et al. Matrix metalloproteinase and tissue inhibitor expression in atherosclerotic and nonatherosclerotic thoracic aortic aneurysms. J Thorac Cardiovasc Surg 2007; 133 (01) 155-161
• 44 Boyum J, Fellinger EK, Schmoker JD. , et al. Matrix metalloproteinase activity in thoracic aortic aneurysms associated with bicuspid and tricuspid aortic valves. J Thorac Cardiovasc Surg 2004; 127 (03) 686-691
• 45 Wang Y, Wu B, Dong L, Wang C, Wang X, Shu X. Circulating matrix metalloproteinase patterns in association with aortic dilatation in bicuspid aortic valve patients with isolated severe aortic stenosis. Heart Vessels 2016; 31 (02) 189-197
• 46 LeMaire SA, Wang X, Wilks JA. , et al. Matrix metalloproteinases in ascending aortic aneurysms: bicuspid versus trileaflet aortic valves. J Surg Res 2005; 123 (01) 40-48
• 47 Mohamed SA, Noack F, Schoellermann K. , et al. Elevation of matrix metalloproteinases in different areas of ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves. ScientificWorldJournal 2012; 2012: 806261
• 48 Ikonomidis JS, Ruddy JM, Benton Jr SM. , et al. Aortic dilatation with bicuspid aortic valves: cusp fusion correlates to matrix metalloproteinases and inhibitors. Ann Thorac Surg 2012; 93 (02) 457-463
• 49 Rabkin SW. Differential expression of MMP-2, MMP-9 and TIMP proteins in thoracic aortic aneurysm - comparison with and without bicuspid aortic valve: a meta-analysis. Vasa 2014; 43 (06) 433-442
• 50 Tzemos N, Lyseggen E, Silversides C. , et al. Endothelial function, carotid-femoral stiffness, and plasma matrix metalloproteinase-2 in men with bicuspid aortic valve and dilated aorta. J Am Coll Cardiol 2010; 55 (07) 660-668
• 51 Padang R, Bannon PG, Jeremy R. , et al. The genetic and molecular basis of bicuspid aortic valve associated thoracic aortopathy: a link to phenotype heterogeneity. Ann Cardiothorac Surg 2013; 2 (01) 83-91
• 52 Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116 (02) 281-297
• 53 Boon RA, Dimmeler S. MicroRNAs and aneurysm formation. Trends Cardiovasc Med 2011; 21 (06) 172-177
• 54 Liu G, Huang Y, Lu X. , et al. Identification and characteristics of microRNAs with altered expression patterns in a rat model of abdominal aortic aneurysms. Tohoku J Exp Med 2010; 222 (03) 187-193
• 55 Elia L, Quintavalle M, Zhang J. , et al. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ 2009; 16 (12) 1590-1598
• 56 Liao M, Zou S, Weng J. , et al. A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis. J Vasc Surg 2011; 53 (05) 1341-1349.e3
• 57 Jones JA, Stroud RE, O'Quinn EC. , et al. Selective microRNA suppression in human thoracic aneurysms: relationship of miR-29a to aortic size and proteolytic induction. Circ Cardiovasc Genet 2011; 4 (06) 605-613
• 58 Boon RA, Seeger T, Heydt S. , et al. MicroRNA-29 in aortic dilation: implications for aneurysm formation. Circ Res 2011; 109 (10) 1115-1119
• 59 Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation 2010; 121 (08) 1022-1032
• 60 Pannu H, Fadulu VT, Chang J. , et al. Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation 2005; 112 (04) 513-520
• 61 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 (02) 389-394
• 62 Hillebrand M, Millot N, Sheikhzadeh S. , et al. Total serum transforming growth factor-β1 is elevated in the entire spectrum of genetic aortic syndromes. Clin Cardiol 2014; 37 (11) 672-679
• 63 Vignaud H, Cullin C, Bouchecareilh M. Alpha-1 antitrypsin deficiency: a model of alteration of protein homeostasis or proteostasis [in French]. Rev Mal Respir 2015; 32 (10) 1059-1071
• 64 Schachner T, Golderer G, Sarg B. , et al. The amounts of alpha 1 antitrypsin protein are reduced in the vascular wall of the acutely dissected human ascending aorta. Eur J Cardiothorac Surg 2010; 37 (03) 684-690
• 65 Kilickesmez KO, Abaci O, Kocas C. , et al. Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve. Heart Vessels 2012; 27 (04) 391-397
• 66 Vizzardi E, Corda L, Pezzali N. , et al. Elastic properties of the ascending aorta in patients with α1-antitrypsin deficiency (Z homozygotes). Heart 2012; 98 (18) 1354-1358
• 67 Böger RH. Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials. Vasc Med 2005; 10 (02) (Suppl. 01) S19-S25
• 68 Böger RH, Sullivan LM, Schwedhelm E. , et al. Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation 2009; 119 (12) 1592-1600
• 69 Schnabel R, Blankenberg S, Lubos E. , et al. Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 2005; 97 (05) e53-e59
• 70 Hofmann MA, Drury S, Fu C. , et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 1999; 97 (07) 889-901
• 71 Yan SD, Zhu H, Zhu A. , et al. Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis. Nat Med 2000; 6 (06) 643-651
• 72 Yan SF, Ramasamy R, Schmidt AM. The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res 2010; 106 (05) 842-853
• 73 Cuccurullo C, Iezzi A, Fazia ML. , et al. Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes. Arterioscler Thromb Vasc Biol 2006; 26 (12) 2716-2723
• 74 Schmidt AM, Yan SD, Yan SF, Stern DM. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 2001; 108 (07) 949-955
• 75 Zhang F, Kent KC, Yamanouchi D. , et al. Anti-receptor for advanced glycation end products therapies as novel treatment for abdominal aortic aneurysm. Ann Surg 2009; 250 (03) 416-423
• 76 Hofmann Bowman M, Wilk J, Heydemann A. , et al. S100A12 mediates aortic wall remodeling and aortic aneurysm. Circ Res 2010; 106 (01) 145-154
• 77 Das D, Gawdzik J, Dellefave-Castillo L. , et al. S100A12 expression in thoracic aortic aneurysm is associated with increased risk of dissection and perioperative complications. J Am Coll Cardiol 2012; 60 (08) 775-785
• 78 Lotze MT, Tracey KJ. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 2005; 5 (04) 331-342
• 79 Kohno T, Anzai T, Kaneko H. , et al. High-mobility group box 1 protein blockade suppresses development of abdominal aortic aneurysm. J Cardiol 2012; 59 (03) 299-306
• 80 Yamagishi S, Adachi H, Nakamura K. , et al. Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects. Metabolism 2006; 55 (09) 1227-1231