Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208

Author(s)

Reno Soci, Ursula Paula ; Fernandes, Tiago ; Barauna, Valerio Garrone ; Hashimoto, Nara Yumi ; Alves Mota, Gloria de Fatima ; Rosa, Kaleizu Teodoro ; Irigoyen, Maria Claudia ; Philips, Michael Ian ; de Oliveira, Edilamar Menezes

• Document type: Journal article
• Source: Clinical Science; v. 130, n. 22, p. 2005-2015, NOV 1 2016.
• Web of Science Citations: 11

Abstract

Aerobic exercise-induced cardiac hypertrophy (CH) is a physiological response involving accurate orchestration of gene and protein expression of contractile and metabolic components. The microRNAs: miR-208a, miR-208b and miR-499 are each encoded by a myosin gene and thus are also known as `MyomiRs', regulating several mRNA targets that in turn regulate CH and metabolic pathways. To understand the role of myomiRs in the fine-tuning of cardiac myosin heavy chain (MHC) isoform expression by exercise training-induced physiological hypertrophy, Wistar rats were subjected to two different swim training protocols. We observed that high-volume swim training (T2), improved cardiac diastolic function, induced CH and decreased the expression of miR-208a and miR-208b. Consequently, the increased expression of their targets, sex determining region y-related transcription factor 6 (Sox6), Med13, Pur beta, specificity proteins (Sp)/Kruppel-like transcription factor 3 (SP3) and HP1 beta (heterochromatin protein 1 beta) was more prominent in T2, thus converging to modulate cardiac metabolic and contractile adaptation by exercise training, with an improvement in the alpha-MHC/beta-MHC ratio, bypassing the increase in PPAR beta and histone deacetylase (HDAC) class I and II regulation. Altogether, we conclude that high-volume swim training finely assures physiological cardiac remodelling by epigenetic regulation of myomiRs, because inhibition of miR-208a and miR-208b increases the expression of their target proteins and stimulates the interaction among metabolic, contractile and epigenetic genes. (AU)

• FAPESP's process: 14/50673-4 - A new therapeutic approach to arterial repair and regeneration by exercise training and microRNAs targeted to vasorin
• Grantee: Edilamar Menezes de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants