Abstract P1003: Expression Of Circulating Atherosclerosis-associated Micrornas In Pre- And Post-menopausal Obese Women: Response To Physical Exercise

Abstract

Atherosclerosis is the basic mechanism of cardiovascular disease, a major cause of mortality. It involves the interaction of environmental factors, such as obesity, and genetics, while exercise is a major risk modifier. Despite its higher prevalence in men, women have a worse outcome; however, they are underrepresented in clinical trials. MicroRNAs (miRs) are gene expression regulators of special interest as potential risk markers for complex diseases. We investigated the effect of physical exercise on the expression of circulating miRs in obese pre- and post-menopausal women. For this purpose, we analyzed serum from six women before and after performing a physical exercise protocol (3 x/week for 16 weeks). Samples were selected from women with extreme responses to the exercise protocol. The miRs were extracted using miRNeasy Serum/Plasma Kit and sequenced by mass sequencing on the Ion Torrent PGM platform. Data were analyzed using the CLC Genomics Workbench software. The differently expressed miRs were submitted to in silico analysis to determine the computational prediction of gene targets with the Mirnet tool (version 2.0). Then, the gene ontology of predicted target genes was verified using EnrichR. Altogether, five miRs with increased expression were identified for the menopausal group compared to the non-menopausal group before physical exercise (miR-199a, -222, -186, -4454, and 126). In the non-menopausal group, we identified one miR with increased expression (miR-122) and 4 with reduced expression (miR-29c, Let-7b, -339, and -98) after the exercise protocol. The menopause group showed an increase of 5 miRs (miR-15b, -19a, -107, -103a, 17) and a reduction of 4 (miR-423, -148a, -Let-7i, and -338) induced by exercise. Gene ontology analysis identified several pathways in the atherosclerosis process modulated by physical exercise. Our results showed that exercise induces the expression of circulating miRs that potentially regulates target genes involved in atherosclerosis physiopathology, inflammatory response, oxidative stress, and obesity. The pathways modulated by exercise differ among pre- and post-menopausal obese women, thus potentially impacting the approach of atherosclerosis in women.