Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation

Author(s):Show less -

Freitas, Lunara S. ^{[1, 2]} ; Silveira, Andre C. ^[3] ; Martins, Franco C. ^[4] ; Costa-Hong, Valeria ^[2] ; Lebkuchen, Adriana ^[5] ; Cardozo, Karina H. M. ^[5] ; Bernardes, Fernanda M. ^[2] ; Bortolotto, Luiz A. ^[2] ; Lorenzi-Filho, Geraldo ^[4] ; Oliveira, Edilamar M. ^[3] ; Drager, Luciano F. ^{[6, 2]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hypertens Unit, Inst Heart, Fac Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Lab Biochem & Mol Biol Exercise, Sch Phys Educ & Sports, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sleep Lab, Inst Heart, Fac Med, Sao Paulo - Brazil

^[5] Fleury Grp, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Sch Med, Hypertens Unit, Div Renal, Sao Paulo - Brazil

• Document type: Journal article
• Source: Sleep and Breathing; v. 24, n. 4 JAN 2020.
• Web of Science Citations: 5

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. (AU)

• FAPESP's process: 12/02953-2 - Impact of obstructive sleep apnea and sleep duration on the progression of cardiovascular diseases
• Grantee: Luciano Ferreira Drager
• Support Opportunities: Research Grants - Young Investigators Grants