Fibrosis-Related Gene Expression in Single Ventricle Heart Disease - 23/11/17
Abstract |
Objective |
To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure.
Study design |
Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression.
Results |
Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right ventricular function (38%).
Conclusions |
Fibrosis is not a primary contributor to right ventricular failure in infants and young children with single ventricular heart disease. Additional studies are required to understand whether antifibrotic therapies are beneficial in this population.
Le texte complet de cet article est disponible en PDF.Keywords : hypoplastic left heart syndrome, congenital heart disease, pediatric heart failure, collagen, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs)
Abbreviations : ACEi, Col, ECM, Gal3, miR-29b, MMPs, mRNA, RAAS, ST2L, TGF-β, TIMPs
Plan
| Supported by the Addison Scott Memorial Fund, the Boedecker Foundation Award, the Jack Cooper Millisor Chair in Pediatric Heart Disease, the Children's Hospital Colorado Summer Child Health Internship Program and the following National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) grants: R01 HL107715 (to B.S.), R21 HL113846 (to S.M.), R01 HL126928 (to S.M.), R21 HL097123 (to B.S., C.S., and S.M.). C.S. owns equity in Miragen, Inc. B.S. receives research support from Forest Laboratories, Inc. C.S., B.S, and S.M. are founders and scientific advisors for CoramiR Biomedical, LLC. The other authors declare no conflicts of interest. |
Vol 191
P. 82 - décembre 2017 Retour au numéro
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