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Modulation of cardiac repair after myocardial infarction by the interaction between proteins SPARC, MMP-3 and osteopontin secreted by adipose tissue stem cells.

Grant number: 12/22549-1
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2013
Effective date (End): February 28, 2015
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:José Eduardo Krieger
Grantee:Marcus Vinicius Naghetini dos Santos
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Cardiovascular diseases such as myocardial infarction are the leading cause of death in the world population. The current therapeutic strategies used for the treatment of these diseases, such as coronary artery bypass grafting, angioplasty and medications do not benefit satisfactorily all types of patient making it necessary to develop alternative therapeutic strategies that add up to well-established therapies.Accordingly, the use of stem cells as a source of cardiac cells appears to be a promising approach in the context of tissue regeneration. Stem cells from different sources used in pre-clinical studies have shown the potential to improve ventricular function after injury of the organ. However, unlike previously thought, much evidence suggests that the mechanisms of action of stem cells are weakly bound to transdifferentiation and tissue replacement. The predominant mechanisms of transplanted cells would be linked to paracrine action through the release of bioactive molecules important in the context of cardiac repair after myocardial infarction. Substantial evidence shows that stem cells from different sources may secrete a range of cytokines and pro-angiogenic, anti-apoptotic and cell proliferation proteins important for cardiac repair after injury. In our laboratory we evaluated the secretome of stem cells from adipose tissue subjected to physical and chemical stimuli and tens of bioactive molecules have been identified with therapeutic potential in the context of cardiac ischemia. Interestingly, with the aid of bioinformatic tools, we analyze the behavior of interaction between these proteins so that we can suggest some targets based on their pleiotropic characteristics. In other words, we come to an interactive network formed by three proteins, namely, SPARC, MMP-3 and osteopontin, probably have important roles in modulating the course of the pathophysiology of cardiac ischemia. Moreover, when we analyzed the database of the transcriptome and proteome of the ischemic heart, we found that the abovementioned factors are expressed in the condition of injury and participate in the activation of pathways important in cardiac repair. Together, the cross-talking between molecules secreted by adult stem cells and those expressed by the heart as a result of ischemic damage, it is a promising approach to identify new paths of investigation of mechanisms that can be explored therapeutically.Based on this, this proposal aims to evaluate the interactive effect of MMP-3, osteopontin and SPARC in modulating the process of cardiac repair after myocardial infarction.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SANTOS, Marcus Vinicius Naghetini dos. Anti-fibrotic effect of SPARC protein in cardiac fibroblasts (Potential mediator of the benefits associated with stem cell transplantation derived from adipose tissue post-myocardial infarction). 2015. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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