Lunara S Freitas1,2, André C Silveira3, Franco C Martins4, Valéria Costa-Hong2, Adriana Lebkuchen5, Karina H M Cardozo5, Fernanda M Bernardes2, Luiz A Bortolotto2, Geraldo Lorenzi-Filho4, Edilamar M Oliveira3, Luciano F Drager6,7. 1. Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 2. Hypertension Unit, Heart Institute, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 3. Laboratory of Biochemistry and Molecular Biology of the Exercise, School of Physical Education and Sports, University of São Paulo, São Paulo, Brazil. 4. Sleep Laboratory, Heart Institute, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 5. Fleury Group, São Paulo, Brazil. 6. Hypertension Unit, Heart Institute, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. luciano.drager@incor.usp.br. 7. Hypertension Unit, Renal Division, University of São Paulo Medical School, São Paulo, Brazil. luciano.drager@incor.usp.br.
Abstract
PURPOSE: Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. METHODS: We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group (n = 6), mild OSA group (n = 12), moderate OSA group (n = 15), and severe OSA group (n = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). RESULTS: The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 (ß = 68.4; EP = 29.8; p = 0.02) and miR-320e (ß = 76.1; EP = 31.3; p = 0.02). CONCLUSION: Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.
PURPOSE: Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. METHODS: We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group (n = 6), mild OSA group (n = 12), moderate OSA group (n = 15), and severe OSA group (n = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). RESULTS: The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 (ß = 68.4; EP = 29.8; p = 0.02) and miR-320e (ß = 76.1; EP = 31.3; p = 0.02). CONCLUSION: Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.
Authors: Lei Gao; Andrew S P Lim; Patricia M Wong; Arlen Gaba; Longchang Cui; Lei Yu; Aron S Buchman; David A Bennett; Kun Hu; Peng Li Journal: Nat Sci Sleep Date: 2020-05-27
Authors: Philip Roger Goody; Lisa Nachtsheim; Mohammed Rabiul Hosen; Miriam von Krosigk; Dominik Christmann; Jens Peter Klussmann; Andreas Zietzer; Nils Breitrück; Felix Jansen; Stefanie Jansen Journal: PLoS One Date: 2022-03-04 Impact factor: 3.240