Role of microRNA-146ª and its vasorine target gene in renovation of the carotid Artery after catheter injury ballon: therapeutic effect of aerobic physical training

Author(s)

Noemy Pinto Pereira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2020-04-28

Examining board members

Edilamar Menezes de Oliveira; Eliana Hiromi Akamine; Valerio Garrone Barauna; Maria Urbana Pinto Brandão Rondon

• Advisor: Edilamar Menezes de Oliveira; Tiago Fernandes

Abstract

Restenosis is a fibroproliferative response that occurs on the vessel wall after a mechanical injury, usually followed by the angioplasty procedure, causing vascular obstruction. The remodeling of the vessel, caused by mechanical injury, causes proliferation, growth, and migration of vascular smooth muscle cells from the media layer to the intima layer, accompanied by fibrosis, causing neointima and narrowing of the lumen vascular. In this type of vascular injury microRNAs (miRNAs) have been widely studied as biomarkers and gene therapy, opening therapeutic perspectives for the treatment of fibroproliferative diseases where the decrease in the expression of miR-146a is a highlight in this type of disease. The miRNA expression can be modulated by exercise training (ET), and it has been studied as non-pharmacological therapy for cardiovascular diseases, promoting several adaptations. Therefore, our aim was to evaluate the restenosis timeline and verify the therapeutic role of aerobic ET in the regression of neointima formation, decreasing the expression of miRNA- 146a and increasing the expression of its vasorin target (VASN) in the control of restenosis and also evaluate molecular mechanisms related to the increase in vascular neointima such as: TGF- β (Transforming Growth Factor Beta), PCNA (Proliferating Cell Nuclear Antigen proliferation index), ADAM-17 (metalloprotease 17), NF-κβ (Nuclear Kappa Factor Beta) and KLF4 (Krüppel-Like Factor 4). For this, we used an aerobic ET protocol (swimming) of moderate intensity, with four experimental groups of Wistar rats: injured with balloon catheter and trained (LT), trained sham (ST) and their respective controls, injured with balloon catheter and sedentary (LS) and sedentary Sham (SS). It was possible to observe that there was an increase in the physical capacity of the animals that went through the swimming ET protocol, as well as a maintenance of body mass and systolic and mean arterial pressure. It was also possible to observe that the ET was able to prevent the exacerbated formation of vascular neointima and capable of maintaining the diameter of the lumen. Regarding the molecular mechanisms involved in the prevention of neointima, it was observed that aerobic ET modulates miRNA 146a, where there was a reduction in it. We observed that there was an increase in VASN gene and protein expression. This leads us to understand that ET was able to prevent restenosis by increasing the expression of VASN, which in turn directly inhibits the activation of the inflammatory pathways that begins with TGF-β activation and which activates several inflammatory cytokines. Making aerobic ET viable for the prevention of exacerbated formation of vascular neointima (AU)

• FAPESP's process: 16/26156-5 - Role of microRNA-146a and its target gene vasorin in the carotid artery remodeling after catheter balloon injury: therapeutic effect of aerobic physical training
• Grantee: Noemy Pinto Pereira
• Support Opportunities: Scholarships in Brazil - Master