Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements

Kristian C. Becker; Lydia Coulter Kwee; Megan L. Neely; Elizabeth Grass; Joseph A. Jakubowski; Keith A.A. Fox; Harvey D. White; Simon G. Gregory; Paul A. Gurbel; Leonardo de Pinto Carvalho; Richard C. Becker; E. Magnus Ohman; Matthew T. Roe; Svati H. Shah; Mark Y. Chan

doi:10.1038/s41598-020-63263-6

Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements

Kristian C. Becker
, Lydia Coulter Kwee
, Megan L. Neely
, Elizabeth Grass
, Joseph A. Jakubowski
, Keith A.A. Fox
, Harvey D. White
, Simon G. Gregory
, Paul A. Gurbel
, Leonardo de Pinto Carvalho
, Richard C. Becker
, E. Magnus Ohman
, Matthew T. Roe
, Svati H. Shah
, Mark Y. Chan

Icahn School of Medicine at Mount Sinai
Duke University
Eli Lilly
University of Edinburgh
Auckland District Health Board
Inova Heart & Vascular Institute
Hospital Israelita Albert Einstein
University of Cincinnati
National University of Singapore

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted & targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91–1.27, p-value: 0.004–0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: −0.09–0.22, p-value: 0.004–0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with PR in the TRILOGY-ACS and independent Singapore post-ACS cohorts, suggesting the measurement of circulating microRNA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.

Original language	English
Article number	6169
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-63263-6
State	Published - 1 Dec 2020
Externally published	Yes

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Becker, K. C., Kwee, L. C., Neely, M. L., Grass, E., Jakubowski, J. A., Fox, K. A. A., White, H. D., Gregory, S. G., Gurbel, P. A., Carvalho, L. D. P., Becker, R. C., Magnus Ohman, E., Roe, M. T., Shah, S. H., & Chan, M. Y. (2020). Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements. Scientific Reports, 10(1), Article 6169. https://doi.org/10.1038/s41598-020-63263-6

@article{6c838b4066fb4f07865aec3fc45386d0,

title = "Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements",

abstract = "Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted \& targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91{\textendash}1.27, p-value: 0.004{\textendash}0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: −0.09{\textendash}0.22, p-value: 0.004{\textendash}0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with PR in the TRILOGY-ACS and independent Singapore post-ACS cohorts, suggesting the measurement of circulating microRNA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.",

author = "Becker, \{Kristian C.\} and Kwee, \{Lydia Coulter\} and Neely, \{Megan L.\} and Elizabeth Grass and Jakubowski, \{Joseph A.\} and Fox, \{Keith A.A.\} and White, \{Harvey D.\} and Gregory, \{Simon G.\} and Gurbel, \{Paul A.\} and Carvalho, \{Leonardo de Pinto\} and Becker, \{Richard C.\} and \{Magnus Ohman\}, E. and Roe, \{Matthew T.\} and Shah, \{Svati H.\} and Chan, \{Mark Y.\}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41598-020-63263-6",

language = "English",

volume = "10",

journal = "Scientific Reports",

issn = "2045-2322",

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Becker, KC, Kwee, LC, Neely, ML, Grass, E, Jakubowski, JA, Fox, KAA, White, HD, Gregory, SG, Gurbel, PA, Carvalho, LDP, Becker, RC, Magnus Ohman, E, Roe, MT, Shah, SH & Chan, MY 2020, 'Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements', Scientific Reports, vol. 10, no. 1, 6169. https://doi.org/10.1038/s41598-020-63263-6

TY - JOUR

T1 - Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements

AU - Becker, Kristian C.

AU - Kwee, Lydia Coulter

AU - Neely, Megan L.

AU - Grass, Elizabeth

AU - Jakubowski, Joseph A.

AU - Fox, Keith A.A.

AU - White, Harvey D.

AU - Gregory, Simon G.

AU - Gurbel, Paul A.

AU - Carvalho, Leonardo de Pinto

AU - Becker, Richard C.

AU - Magnus Ohman, E.

AU - Roe, Matthew T.

AU - Shah, Svati H.

AU - Chan, Mark Y.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted & targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91–1.27, p-value: 0.004–0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: −0.09–0.22, p-value: 0.004–0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with PR in the TRILOGY-ACS and independent Singapore post-ACS cohorts, suggesting the measurement of circulating microRNA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.

AB - Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted & targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91–1.27, p-value: 0.004–0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: −0.09–0.22, p-value: 0.004–0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with PR in the TRILOGY-ACS and independent Singapore post-ACS cohorts, suggesting the measurement of circulating microRNA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.

UR - https://www.scopus.com/pages/publications/85083247825

U2 - 10.1038/s41598-020-63263-6

DO - 10.1038/s41598-020-63263-6

M3 - Article

C2 - 32277149

AN - SCOPUS:85083247825

SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 6169

ER -

Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements

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