TY - JOUR
T1 - Peripheral Blood RNA Levels of QSOX1 and PLBD1 Are New Independent Predictors of Left Ventricular Dysfunction after Acute Myocardial Infarction
AU - Vanhaverbeke, Maarten
AU - Vausort, Mélanie
AU - Veltman, Denise
AU - Zhang, Lu
AU - Wu, Ming
AU - Laenen, Griet
AU - Gillijns, Hilde
AU - Moreau, Yves
AU - Bartunek, Jozef
AU - Van De Werf, Frans
AU - Devaux, Yvan
AU - Janssens, Stefan
AU - Sinnaeve, Peter R.
N1 - Funding Information:
Research was funded by Research Foundation Flanders—a score grant from the University of Leuven (PF10/014) and the Frans Van de Werf Fund for Clinical Cardiovascular Research. Dr Sinnaeve is a clinical investigator for the Research Foundation Flanders. Dr Janssens is holder of a named chair at KU Leuven, financed by AstraZeneca. The independent validation cohort was supported by the Ministry of Higher Education and Research and the Society for Research on Cardiovascular Diseases of Luxembourg.
Funding Information:
The authors acknowledge all personnel of the cardiac catheterization laboratory and cardiac intensive care unit of the University Hospitals Leuven. We gratefully acknowledge the staff of the microarray facility VIB Nucleomics Core, in particular, Ruth Maes and Wout Van Delm. We furthermore thank Margaretha Van Ker-rebroeck and Sofie Van Soest for the assistance during the animal experiments. We thank Christelle Nicolas, Bernadette Leners, Torkia Lalem, and Mara Luchetti for their contribution in the validation study. This article is based on collaboration supported by the European Union Cooperation in Science and Technology Action CardioRNA CA17129. Dr Vanhaverbeke, Dr Bartunek, Dr Van De Werf, Dr Janssens, and Dr Sinnaeve contributed to the study design; Dr Vanhaverbeke, Dr Wu, G. Laenen, H. Gillijns, Dr Moreau, Dr Janssens, and Dr Sinnaeve contributed to methodology; Dr Vanhaverbeke, D. Veltman, H. Gillijns, Dr Janssens, and Dr Sinnaeve enrolled patients and performed follow-up; porcine experiments were performed by Dr Vanhaverbeke, D. Veltman, Dr Wu, and H. Gillijns; data from the validation cohort was provided by M. Vausort, L. Zhang and Dr Devaux; data analysis was done by Dr Vanhaverbeke, M. Vausort, D. Veltman, L. Zhang, Dr Wu, G. Laenen, Dr Moreau, Dr Sinnaeve, and Dr Janssens; Dr Vanhaverbeke, M. Vausort, Dr Devaux, Dr Janssens, and Dr Sinnaeve contributed to the writing of the manuscript; all authors performed the revision and editing of the manuscript; and Dr Vanhaverbeke, Dr Van De Werf, Dr Devaux, Dr Janssens, and Dr Sinnaeve contributed to resources and funding acquisition.
Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Background: The identification of patients with acute myocardial infarction (MI) at risk of subsequent left ventricular (LV) dysfunction remains challenging, but it is important to optimize therapies. The aim of this study was to determine the unbiased RNA profile in peripheral blood of patients with acute MI and to identify and validate new prognostic markers of LV dysfunction. Methods: We prospectively enrolled a discovery cohort with acute MI (n=143) and performed whole-blood RNA profiling at different time points. We then selected transcripts on admission that related to LV dysfunction at follow-up and validated them by quantitative polymerase chain reaction in the discovery cohort, in an external validation cohort (n=449), and in a representative porcine MI model with cardiac magnetic resonance-based measurements of infarct size and postmortem myocardial pathology (n=33). Results: RNA profiling in the discovery cohort showed upregulation of genes involved in chemotaxis, IL (interleukin)-6, and NF-κB (nuclear factor-κB) signaling in the acute phase of MI. Expression levels of the majority of these transcripts paralleled the rise in cardiac troponin T and decayed at 30 days. RNA levels of QSOX1, PLBD1, and S100A8 on admission with MI correlated with LV dysfunction at follow-up. Using quantitative polymerase chain reaction, we confirmed that QSOX1 and PLBD1 predicted LV dysfunction (odds ratio, 2.6 [95% CI, 1.1-6.1] and 3.2 [95% CI, 1.4-7.4]), whereas S100A8 did not. In the external validation cohort, we confirmed QSOX1 and PLBD1 as new independent markers of LV dysfunction (odds ratio, 1.41 [95% CI, 1.06-1.88] and 1.43 [95% CI, 1.08-1.89]). QSOX1 had an incremental predictive value in a model consisting of clinical variables and cardiac biomarkers (including NT-proBNP [N-Terminal pro-B-Type natriuretic peptide]). In the porcine MI model, whole-blood levels of QSOX1 and PLBD1 related to neutrophil infiltration in the ischemic myocardium in an infarct size-independent manner. Conclusions: Peripheral blood QSOX1 and PLBD1 in acute MI are new independent markers of LV dysfunction post-MI.
AB - Background: The identification of patients with acute myocardial infarction (MI) at risk of subsequent left ventricular (LV) dysfunction remains challenging, but it is important to optimize therapies. The aim of this study was to determine the unbiased RNA profile in peripheral blood of patients with acute MI and to identify and validate new prognostic markers of LV dysfunction. Methods: We prospectively enrolled a discovery cohort with acute MI (n=143) and performed whole-blood RNA profiling at different time points. We then selected transcripts on admission that related to LV dysfunction at follow-up and validated them by quantitative polymerase chain reaction in the discovery cohort, in an external validation cohort (n=449), and in a representative porcine MI model with cardiac magnetic resonance-based measurements of infarct size and postmortem myocardial pathology (n=33). Results: RNA profiling in the discovery cohort showed upregulation of genes involved in chemotaxis, IL (interleukin)-6, and NF-κB (nuclear factor-κB) signaling in the acute phase of MI. Expression levels of the majority of these transcripts paralleled the rise in cardiac troponin T and decayed at 30 days. RNA levels of QSOX1, PLBD1, and S100A8 on admission with MI correlated with LV dysfunction at follow-up. Using quantitative polymerase chain reaction, we confirmed that QSOX1 and PLBD1 predicted LV dysfunction (odds ratio, 2.6 [95% CI, 1.1-6.1] and 3.2 [95% CI, 1.4-7.4]), whereas S100A8 did not. In the external validation cohort, we confirmed QSOX1 and PLBD1 as new independent markers of LV dysfunction (odds ratio, 1.41 [95% CI, 1.06-1.88] and 1.43 [95% CI, 1.08-1.89]). QSOX1 had an incremental predictive value in a model consisting of clinical variables and cardiac biomarkers (including NT-proBNP [N-Terminal pro-B-Type natriuretic peptide]). In the porcine MI model, whole-blood levels of QSOX1 and PLBD1 related to neutrophil infiltration in the ischemic myocardium in an infarct size-independent manner. Conclusions: Peripheral blood QSOX1 and PLBD1 in acute MI are new independent markers of LV dysfunction post-MI.
KW - biomarkers
KW - gene expression
KW - inflammation
KW - myocardial infarction
KW - ventricular dysfunction, left
UR - http://www.scopus.com/inward/record.url?scp=85076876677&partnerID=8YFLogxK
U2 - 10.1161/CIRCGEN.119.002656
DO - 10.1161/CIRCGEN.119.002656
M3 - Letter
C2 - 31756302
AN - SCOPUS:85076876677
VL - 12
SP - 561
EP - 572
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
SN - 1942-325X
IS - 12
ER -