High blood pressure, cardiac hypertrophy, heart failure and dystrophin glycoprotein complex.

• Grant number: 12/09665-2
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2012
• Effective date (End): January 31, 2013
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal researcher: Cibele Maria Prado Zinni
• Grantee: Rubens Fernando Pedro
• Home 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

The aim of this work is the study of hypertensive heart disease, heart failure and cardiac hypertrophy, and cytoskeletal proteins. Specifically, we will evaluate a group of structural proteins responsible for the connection between the intracellular and extracellular environment and provide structural stability to the cell membrane of the cardiomyocytes. The absence of one or more components of this group of proteins causes progressive muscle degeneration as well as involves the disruption of the physical connection that anchors actin to the subsarcolemmal cytoskeleton and the sarcomeres to the sarcolemma, with consequent loss of function and cell death. The identification of yet unknown molecular mechanisms of mismatch in ventricular hypertrophy induced by hypertension provides new and interesting data. These abnormal parameters emerge as potential therapeutic targets whose modulation might provide beneficial effects in the development of cardiac abnormalities and, very importantly, the morbidity and mortality of these diseases. The student will receive an initial training in biosafety, anesthesia and handling of laboratory animals. Wistar rats will be subjected to abdominal aortic stenosis and divided into two major groups: (I) regression of compensated cardiac hypertrophy, progression to decompensation and decompensated hypertrophy and (ii) prevention of compensated cardiac hypertrophy, and progression to decompensation and decompensated hypertrophy. The animals of group I initiate treatment with different classes of antihypertensive at different times after surgery: 4, 6 and 8 weeks with the drug, captopril, nifedipine, captopril + nefidipina and, three weeks each treatment. The animals of group II initiate treatment 2 days before surgery and are sacrificed at 4, 6 and 8 weeks of surgery. Blood pressure will be measured by cannulating the carotid artery and the animals sacrificed at different periods. Tissues will be collected for histology, immunofluorescence and Western blotting. It will also be assessed cardiac function by echocardiography.

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. Web of Science Citations: 6.