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: 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


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2019 Číslo 12