title: Low MT-CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease.
abstract: Cytochrome oxidase (COX) IV complex regulates energy production in mitochondria. Impaired COX gene expression is related to obesity and type 2 diabetes mellitus, but whether it is directly related to the incidence of cardiovascular events is unknown. We investigated whether COX gene expression in monocytes is predictive for cardiovascular events in coronary artery disease patients. To avoid monocyte isolation from fresh blood, we then aimed to validate our findings in monocyte-derived microvesicles isolated from plasma.
  
  
  
  We enrolled 142 consecutive patients undergoing diagnostic coronary angiography between June 2010 and January 2011 and followed 67 patients with stable coronary artery disease prospectively for at least 3 years. Twenty-two patients experienced a new cardiovascular event (32.8%). Circulating CD14+monocytes and microvesicles were isolated with magnetic beads, and COX mRNA levels were measured with quantitative polymerase chain reaction, after normalization with 5 validated house-keeping genes. Patients in the lowest tertile of mitochondrial cytochrome oxidase, subunit I (MT-COI) in monocytes at baseline had a higher risk for developing a new event after adjusting for age, sex, (ex)smoking, body mass index, blood pressure, diabetes mellitus, low-density lipoprotein- and high-density lipoprotein-cholesterol, triglycerides, high-sensitivity C-reactive protein, interleukin-6, and number of diseased vessels (harzard ratio [HR], 3.95; 95% CI, 1.63-9.57). Patients in the lowest tertile of MT-COI in monocyte-specific microvesicles had also a higher risk of developing a new event (adjusted HR, 5.00; 95% CI, 1.77-14).
  
  
  
  In the current blinded study, low MT-COI in monocytes of coronary artery disease patients identifies a population at risk for new cardiovascular events. For the first time, we show that signatures in monocyte-specific microvesicles in plasma have similar predictive properties.
authors.affiliation: Atherosclerosis and Metabolism Unit, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium paul.holvoet@med.kuleuven.be.
authors.forename: Paul
authors.initials: P
authors.lastname: Holvoet
authors.affiliation: Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Vanhaverbeke
authors.affiliation: Department of Oncology, KU Leuven, Leuven, Belgium.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bloch
authors.affiliation: VIB BIO Imaging Core, KU Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Baatsen
authors.affiliation: Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Sinnaeve
authors.affiliation: Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
mesh_terms: D002318:Cardiovascular Diseases / Q000401:mortality; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D051863:Host Cell Factor C1; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction; D020521:Stroke / Q000453:epidemiology / Q000378:metabolism
chemical_list: D051863:Host Cell Factor C1; D012333:RNA, Messenger; D003576:Electron Transport Complex IV; C581860:cytochrome c oxidase subunit I, human
keywords: blood cell; cardiovascular events; gene; ischemia; microvesicles