Genetic variants of HIF1α are associated with right ventricular fibrotic load in repaired tetralogy of Fallot patients: a cardiovascular magnetic resonance study.
Cardiac Surgical Procedures
Contrast Media
/ administration & dosage
Female
Fibrosis
Gadolinium DTPA
/ administration & dosage
Genetic Predisposition to Disease
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Infant
Infant, Newborn
Magnetic Resonance Imaging, Cine
Male
Phenotype
Polymorphism, Single Nucleotide
Predictive Value of Tests
Retrospective Studies
Risk Factors
Tetralogy of Fallot
/ diagnostic imaging
Treatment Outcome
Ventricular Function, Right
Ventricular Remodeling
Cardiovascular magnetic resonance imaging
Fibrosis
HIF1α
Right ventricular ejection fraction
Right ventricular end-diastolic volume
Tetralogy of Fallot
Journal
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
ISSN: 1532-429X
Titre abrégé: J Cardiovasc Magn Reson
Pays: England
ID NLM: 9815616
Informations de publication
Date de publication:
19 08 2019
19 08 2019
Historique:
received:
21
01
2019
accepted:
14
06
2019
entrez:
20
8
2019
pubmed:
20
8
2019
medline:
6
5
2020
Statut:
epublish
Résumé
Studies suggest that right ventricular (RV) fibrosis is associated with RV remodeling and long-term outcomes in patients with tetralogy of Fallot (TOF). Pre-operative hypoxia may increase expression of hypoxia inducible factor-1-alpha (HIF1α) and promote transforming growth factor β1 (TGFβ1)-mediated fibrosis. We hypothesized that there would be associations between: (1) RV fibrosis and RV function, (2) HIF1α variants and RV fibrosis, and (3) HIF1α variants and RV function among post-surgical TOF cases. We retrospectively measured post-surgical fibrotic load (indexed volume and fibrotic score) from 237 TOF cases who had existing cardiovascular magnetic resonance imaging using late gadolinium enhancement (LGE), and indicators of RV remodeling (i.e., ejection fraction [RVEF] and end-diastolic volume indexed [RVEDVI]). Genetic data were available in 125 cases. Analyses were conducted using multivariable linear mixed-effects regression with a random intercept and multivariable generalized Poisson regression with a random intercept. Indexed fibrotic volume and fibrotic score significantly decreased RVEF by 1.6% (p = 0.04) and 0.9% (p = 0.03), respectively. Indexed fibrotic volume and score were not associated with RVEDVI. After adjusting for multiple comparisons, 6 of the 48 HIF1α polymorphisms (representing two unique signals) were associated with fibrotic score. None of the HIF1α polymorphisms were associated with indexed fibrotic volume, RVEDVI, or RVEF. The association of some HIF1α polymorphisms and fibrotic score suggests that HIF1α may modulate the fibrotic response in TOF.
Sections du résumé
BACKGROUND
Studies suggest that right ventricular (RV) fibrosis is associated with RV remodeling and long-term outcomes in patients with tetralogy of Fallot (TOF). Pre-operative hypoxia may increase expression of hypoxia inducible factor-1-alpha (HIF1α) and promote transforming growth factor β1 (TGFβ1)-mediated fibrosis. We hypothesized that there would be associations between: (1) RV fibrosis and RV function, (2) HIF1α variants and RV fibrosis, and (3) HIF1α variants and RV function among post-surgical TOF cases.
METHODS
We retrospectively measured post-surgical fibrotic load (indexed volume and fibrotic score) from 237 TOF cases who had existing cardiovascular magnetic resonance imaging using late gadolinium enhancement (LGE), and indicators of RV remodeling (i.e., ejection fraction [RVEF] and end-diastolic volume indexed [RVEDVI]). Genetic data were available in 125 cases. Analyses were conducted using multivariable linear mixed-effects regression with a random intercept and multivariable generalized Poisson regression with a random intercept.
RESULTS
Indexed fibrotic volume and fibrotic score significantly decreased RVEF by 1.6% (p = 0.04) and 0.9% (p = 0.03), respectively. Indexed fibrotic volume and score were not associated with RVEDVI. After adjusting for multiple comparisons, 6 of the 48 HIF1α polymorphisms (representing two unique signals) were associated with fibrotic score. None of the HIF1α polymorphisms were associated with indexed fibrotic volume, RVEDVI, or RVEF.
CONCLUSION
The association of some HIF1α polymorphisms and fibrotic score suggests that HIF1α may modulate the fibrotic response in TOF.
Identifiants
pubmed: 31422771
doi: 10.1186/s12968-019-0555-2
pii: 10.1186/s12968-019-0555-2
pmc: PMC6699069
doi:
Substances chimiques
Contrast Media
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Gadolinium DTPA
K2I13DR72L
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
51Subventions
Organisme : NHLBI NIH HHS
ID : P50 HL074731
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007915
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1TR000003
Pays : United States
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