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.

Autor: Holvoet P; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium., Klocke B; Intrexon Bioinformatics Germany, Munich, Germany., Vanhaverbeke M; Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium., Menten R; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium., Sinnaeve P; Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium., Raitoharju E; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.; Finnish Cardiovascular Research Centre, Faculty of Medicine and Life Sciences University of Tampere, Tampere, Finland., Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.; Finnish Cardiovascular Research Centre, Faculty of Medicine and Life Sciences University of Tampere, Tampere, Finland., Oksala N; Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland., Zinser C; Intrexon Bioinformatics Germany, Munich, Germany., Janssens S; Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium., Sipido K; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium., Lyytikainen LP; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.; Finnish Cardiovascular Research Centre, Faculty of Medicine and Life Sciences University of Tampere, Tampere, Finland., Cagnin S; Department of Biology, CRIBI Biotechnology Centre, Padova, Italy.; CIR-Myo Myology Centre, University of Padova, Padova, Italy.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Dec 10; Vol. 14 (12), pp. e0225621. Date of Electronic Publication: 2019 Dec 10 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0225621
Abstrakt: 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.
Competing Interests: We have the following interests: Bernward Klocke is employed by Intrexon Bioinformatics Germany which was hired by KU Leuven to deliver service in modeling. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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