Abstract
Background:
Tetralogy of Fallot patients with pulmonary atresia (TOF/PA) present a pulmonary blood supply directly from aortic collateral arteries. Major aorto-pulmonary collateral arteries (MAPCAs) present substantial clinical and surgical management challenges. Surgical operations to reestablish and promote further development of a pulmonary arterial connection preferentially utilize MAPCAs for reconstruction of central pulmonary arteries. However, the propensity of some MAPCAs to develop stenosis rather than growth may impair the response to reconstructions.
Methods:
Probe sets prepared from MAPCAs, PA, and aorta mRNA were used to interrogate human genome microarrays. We compared expression differences between pairs of the three vessels to determine whether MAPCAs display distinct expression patterns.
Results:
Functional clustering analysis identified differences in gene expression, which were further analyzed by gene ontology classification. A subset of highly regulated genes was validated using quantitative PCR. Expression differences among vessel types were observed for multiple gene classes. Of note, we observed that MAPCAs differentially express several genes at much higher levels than either PA or aorta.
Conclusion:
MAPCAs differ from PA or aorta by significantly altered levels in gene expression, suggesting a transcriptional basis for their physiology that will guide a further understanding of the pathobiology of MAPCAs and TOF.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Reinhartz O, Reddy VM, Petrossian E, et al. Unifocalization of major aortopulmonary collaterals in single-ventricle patients. Ann Thorac Surg 2006;82:934–8; discussion 938–9.
Tchervenkov CI, Salasidis G, Cecere R, et al. One-stage midline unifocalization and complete repair in infancy versus multiple-stage unifocalization followed by repair for complex heart disease with major aortopulmonary collaterals. J Thorac Cardiovasc Surg 1997;114:727–35; discussion 735–7.
Boshoff D, Gewillig M . A review of the options for treatment of major aortopulmonary collateral arteries in the setting of tetralogy of Fallot with pulmonary atresia. Cardiol Young 2006;16:212–20.
Nørgaard MA, Alphonso N, Cochrane AD, Menahem S, Brizard CP, d’Udekem Y . Major aorto-pulmonary collateral arteries of patients with pulmonary atresia and ventricular septal defect are dilated bronchial arteries. Eur J Cardiothorac Surg 2006;29:653–8.
Thiene G, Frescura C, Bortolotti U, Del Maschio A, Valente M . The systemic pulmonary circulation in pulmonary atresia with ventricular septal defect: concept of reciprocal development of the fourth and sixth aortic arches. Am Heart J 1981;101:339–44.
Haworth SG . Collateral arteries in pulmonary atresia with ventricular septal defect. A precarious blood supply. Br Heart J 1980;44:5–13.
Reddy VM, Liddicoat JR, Hanley FL . Midline one-stage complete unifocalization and repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. J Thorac Cardiovasc Surg 1995;109:832–44; discussion 844–5.
Carotti A, Di Donato RM, Squitieri C, Guccione P, Catena G . Total repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals: an integrated approach. J Thorac Cardiovasc Surg 1998;116:914–23.
Macartney F, Deverall P, Scott O . Haemodynamic characteristics of systemic arterial blood supply to the lungs. Br Heart J 1973;35:28–37.
Malhotra SP, Hanley FL . Surgical management of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals: a protocol-based approach. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2009:145–51.
Moritz A, Marx M, Wollenek G, Domanig E, Wolner E . Complete repair of PA-VSD with diminutive or discontinuous pulmonary arteries by transverse thoracosternotomy. Ann Thorac Surg 1996;61:646–50.
Reddy VM, Petrossian E, McElhinney DB, Moore P, Teitel DF, Hanley FL . One-stage complete unifocalization in infants: when should the ventricular septal defect be closed? J Thorac Cardiovasc Surg 1997;113:858–66; discussion 866–8.
Bull K, Somerville J, Ty E, Spiegelhalter D . Presentation and attrition in complex pulmonary atresia. J Am Coll Cardiol 1995;25:491–9.
Hanley FL . MAPCAs, bronchials, monkeys, and men. Eur J Cardiothorac Surg 2006;29:643–4.
David L, Feige JJ, Bailly S . Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev 2009;20:203–12.
Nakanishi K, Saito Y, Azuma N, Sasajima T . Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia. J Vasc Surg 2013;57:182–93, 193.e1–10.
Faggioni M, Knollmann BC . Calsequestrin 2 and arrhythmias. Am J Physiol Heart Circ Physiol 2012;302:H1250–60.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Tables
(DOC 230 kb)
Rights and permissions
About this article
Cite this article
Ma, X., Barboza, L., Siyahian, A. et al. Tetralogy of Fallot: aorto-pulmonary collaterals and pulmonary arteries have distinctly different transcriptomes. Pediatr Res 76, 341–346 (2014). https://doi.org/10.1038/pr.2014.101
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2014.101


