RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease
Autoři:
Paul Holvoet aff001; Bernward Klocke aff002; Maarten Vanhaverbeke aff003; Roxane Menten aff001; Peter Sinnaeve aff003; Emma Raitoharju aff004; Terho Lehtimäki aff004; Niku Oksala aff006; Christian Zinser aff002; Stefan Janssens aff003; Karin Sipido aff001; Leo-Pekka Lyytikainen aff004; Stefano Cagnin aff007
Působiště autorů:
Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
aff001; Intrexon Bioinformatics Germany, Munich, Germany
aff002; Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium
aff003; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
aff004; Finnish Cardiovascular Research Centre, Faculty of Medicine and Life Sciences University of Tampere, Tampere, Finland
aff005; Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland
aff006; Department of Biology, CRIBI Biotechnology Centre, Padova, Italy
aff007; CIR-Myo Myology Centre, University of Padova, Padova, Italy
aff008
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0225621
Souhrn
Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted.
Klíčová slova:
Blood – Coronary heart disease – Cytokines – Gene expression – Macrophages – Monocytes – RNA sequencing – Stable coronary artery disease
Zdroje
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