Behavior and correlation between TAK1, Cyld and ITCH complex during the evolution of myocardial infarction

• Grant number: 17/08893-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2017
• End date: July 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcos Ferreira Minicucci
• Grantee: Maisa Ayumi Kimura
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

After myocardial infarction (MI) there are several changes in ventricular architecture, including the infarcted and non-infarcted areas. This process is known as cardiac remodeling (CR). Among several factors associated with CR, we highlight the inflammatory process and the immune system. It is interesting to notice that an exacerbated inflammatory response in the initial phase after MI is associated with poor outcomes. However, clinical studies that evaluated the effects of anti-inflammatory and anti-TNF drugs after MI did not show any benefit. The results of these studies reinforce the key role of inflammation in tissue repair, and the inflammation suppression, at least in the acute phase, could lead to worse outcomes. Thus, improve the knowledge of inflammation after MI is a critical step. In this scenario, it is important to highlight the role of TGF-²-activated kinase 1 (TAK1). TAK1 is a member of the MAPK kinase family, and has been identified originally in 1995, as a protein activated by TGF-² and bone morphogenetic protein. However, recent studies showed the fundamental role of TAK1 in the regulation of pathways related to inflammatory and immune response, such as NF-kB and activator protein-1 (AP-1). There are several post-translational modifications that modulate the activation of TAK1, among them the ubiquitination process. Cyld and ITCH complex (Cyld-itchy E3 ligase) are proteins that prevent TAK1 activation promoting its deubiquitination. Although, the behavior of TAK1 in the later phase of post-MI CR and the correlation between TAK1 with Cyld and ITCH complex has not been evaluated. Thus, we believe that TAK1 expression will be increased in the initial phase after MI, and that it will decrease, but maintaining higher values compared to control group in the chronical phase. In addition, we believe that the expression of Cyld and ITCH complex will be reduced in the initial phase and will increase in the chronical phase after MI. (AU)