Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease
Background 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 expre...
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Wiley
2016-12-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.116.004207 |
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| author | Paul Holvoet Maarten Vanhaverbeke Katarzyna Bloch Pieter Baatsen Peter Sinnaeve Stefan Janssens |
| author_facet | Paul Holvoet Maarten Vanhaverbeke Katarzyna Bloch Pieter Baatsen Peter Sinnaeve Stefan Janssens |
| author_sort | Paul Holvoet |
| collection | DOAJ |
| description | Background 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. Methods and Results 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). Conclusions 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. |
| format | Article |
| id | doaj-art-1024ee562f62405c8dfc85d1d091744e |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2016-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-1024ee562f62405c8dfc85d1d091744e2025-08-20T03:29:09ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-12-0151210.1161/JAHA.116.004207Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery DiseasePaul Holvoet0Maarten Vanhaverbeke1Katarzyna Bloch2Pieter Baatsen3Peter Sinnaeve4Stefan Janssens5Atherosclerosis and Metabolism Unit Department of Cardiovascular Sciences KU Leuven Leuven BelgiumDepartment of Clinical Cardiology UZ Leuven Leuven BelgiumDepartment of Oncology KU Leuven Leuven BelgiumVIB BIO Imaging Core KU Leuven Leuven BelgiumDepartment of Clinical Cardiology UZ Leuven Leuven BelgiumDepartment of Clinical Cardiology UZ Leuven Leuven BelgiumBackground 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. Methods and Results 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). Conclusions 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.https://www.ahajournals.org/doi/10.1161/JAHA.116.004207blood cellcardiovascular eventsgeneischemiamicrovesicles |
| spellingShingle | Paul Holvoet Maarten Vanhaverbeke Katarzyna Bloch Pieter Baatsen Peter Sinnaeve Stefan Janssens Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease blood cell cardiovascular events gene ischemia microvesicles |
| title | Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease |
| title_full | Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease |
| title_fullStr | Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease |
| title_full_unstemmed | Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease |
| title_short | Low MT‐CO1 in Monocytes and Microvesicles Is Associated With Outcome in Patients With Coronary Artery Disease |
| title_sort | low mt co1 in monocytes and microvesicles is associated with outcome in patients with coronary artery disease |
| topic | blood cell cardiovascular events gene ischemia microvesicles |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.116.004207 |
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