The role of TGF-B in the transition of compensated to decompensated heart hypertrophy in rats submitted to abdominal aorta constriction

• Grant number: 14/07527-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2014
• End date: December 31, 2014
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Cibele Maria Prado Zinni
• Grantee: Thayane Rafaela Feola Pizzo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 09/17787-8 - High blood pressure, cardiac hypertrophy, heart failure and dystrophin-glycoprotein complex, AP.JP

Abstract

Cardiac hypertrophy is an adaptive morphological response of the heart to work overload and is an important risk factor for myocardial infarction, heart failure and sudden death. Cardiac hypertrophy in response to pressure overload is initially a beneficial response and the mechanisms responsible for the transition of compensated cardiac hypertrophy or physiological to decompensated hypertrophy or pathological are still partially defined. The fibrosis and hypertrophy of cardiomyocytes are considered the major markers of abnormality in the heart in heart failure. For a long time, changes in cardiomyocytes were attributed as the basic cause of ventricular dysfunction in the hypertrophied heart muscle. In the last decades an interstitial disease in hypertensive heart disease has also been demonstrated. The progressive remodeling of the cardiac muscle, the vessels and the extracellular matrix leads to increased stress on the heart wall, exceeding the compensatory capacity of the heart, leading to subsequent degradation of the extracellular matrix and alterations in the collagen network. These progressive morphological and functional changes in the left ventricle generate decompensate hypertrophy. It has been demonstrated the role of TGF-² peptide (transforming growth factor beta) in the myocardium during hypertrophy and heart failure. TGF-² has been implicated as the main mediator that initiates and ends this tissue repair and that supports the production and development of myocardial fibrosis. The aim of this study is to assess how is the expression of TGF-², type I collagen, type III collagen and integrin in compensated hypertrophy (30d after surgery), evolution/transition from compensated hypertrophy to decompensated (60d after surgery) and hypertrophy decompensated ( 90d after surgery) . This project will provide unprecedented data to characterize mechanistic and subcellular events in the pathogenesis of hypertensive heart disease. These abnormal parameters emerge as potential therapeutic targets whose modulation may provide beneficial effects in the development of cardiac abnormalities.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, DANIELE O.; BLEFARI, VALDECIR; PRADO, FERNANDA P.; SILVA, CARLOS A.; FAZAN, JR., RUBENS; SALGADO, HELIO C.; RAMOS, SIMONE G.; PRADO, CIBELE M.. Reduced expression of adherens and gap junction proteins can have a fundamental role in the development of heart failure following cardiac hypertrophy in rats. Experimental and Molecular Pathology, v. 100, n. 1, p. 167-176, FEB 2016. (09/17787-8, 10/19216-5, 12/09665-2, 09/54010-1, 14/07527-7)