Effect of SPARC protein on collagen production and myofibroblast survival in the context of cardiac ischemia

• Grant number: 12/20360-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2013
• End date: November 30, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Eduardo Krieger
• Grantee: André Silva Franco
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

After cardiac ischemia, there are three stages for tissue replacement of the injured region by repairing tissue rich in collagen - inflammatory, proliferative, and maturation. Myofibroblasts are the cells responsible for the generation of new extracellular matrix (ECM) in the infarcted area and they derive from the activation of cardiac fibroblasts by TGF-² (van den Borne et al., 2010). Given the key role of myofibroblasts in this process, and the adverse effects of continuous and undesirable deposition of collagen in the heart, strategies to modulate the balance between activation and survival of these cells are critical to prevent organ dysfunction. In this sense, modulation of TGF-² signaling is an important subject of study (van den Borne et al., 2010). The SPARC protein participates in the process of maturation and organization of the ECM. It's participation in the activation of TGF-² signaling has been demonstrated in mesangial cells via interaction with the TGF-² receptor (Francki A. et al., 2004). Recently it has been identified among factors released by stem cells from adipose tissue involved in a beneficial effect on cardiac remodeling and cardiac function in infarcted rats (Danoviz et al., 2011). However, this study proposes to investigate the role of SPARC protein in cardiac myofibroblasts and collagen secretion aspects and the survival of these cells. The findings of this study can allow structural treatment proposals of the ischemic heat that will represent again from the clinical point of view.(AU)