Structural and molecular aspects of cardiac muscle from dysfunction to heart failure: expression of metalloproteinases and TIMPs involved in cardiac fibrosis

• Grant number: 14/10855-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2014
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Maeli Dal Pai
• Grantee: Francielle Caroline Mosele
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cardiac Remodeling (CR) is a time-dependent process that promotes cellular and molecular changes, which are manifested by changes in size, shape, and function of the myocardium after the injured, and heart failure (HF) is the final stage of this process. Heart failure is characterized by impaired perfusion of blood from the heart to other body tissues. This is due, in part, to the presence of hypertrophy and fibrosis that occurs in cardiomyocytes, which decrease their propelling activity. These changes in the ECM, commonly found in HF, originate, in part, from the disruption of the balance between the production of active metalloproteinases (MMPs) and their inhibition. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of these MMPs and, therefore, are important regulators of ECM renewal and tissue remodeling. The aim of this study is to evaluate structural and molecular aspects of the heart muscle from dysfunction to HF, in an induced aortic stenosis (AS) model. We will use 32 male Wistar rats (90 to 100g). After 18 and 28 weeks of surgery of AS induction, control animals (Sham) and AS will be submitted to echocardiography to evaluate the ventricular function and sacrificed for the sample collection of the left ventricle, the main affected by the HF, for histochemical and molecular analysis. For histochemical analysis will be used the picrosirius staining for morphology and quantification of collagen in the extracellular matrix. The analysis of gene expression of MMPs 1, 2, and 9 and TIMP 1 and 2 will be performed by RT-qPCR. The results may help in the characterization of genes and miRNAs expressed during the transition between the dysfunction and HF, and point out important miRNAs in the regulation of genes involved in the progression of HF. (AU)