A new therapeutic approach to arterial repair and regeneration by exercise training and microRNAs targeted to vasorin

• Grant number: 14/50673-4
• Support type: Regular Research Grants
• Duration: May 01, 2016 - June 30, 2019
• Field of knowledge: Biological Sciences - Physiology
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Edilamar Menezes de Oliveira
• Grantee: Edilamar Menezes de Oliveira
• Principal investigator abroad: Michael Ianphillips
• Institution abroad: Keck Graduate Institute (KGI), United States
• Home Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The project addresses vascular system and the mechanism of repair after vessel wall injury. The experiments should demonstrate if training exercise plays a role in enhancing repair of adult blood vessel injury and how it may work through the interaction of vasorin and TGF- β pathway on arteries. Vasorin is a cell-surface protein that is reduced after blood vessel injury. It binds to TGF- β which increases fibrosis after vascular injury. Blood vessel repair is a balance of neointimal formation versus fibrogenesis. We hypothesize that inhibition of vasorin which occurs after vascular injury can be overcome by delivering miRNAs targeted to vasorin to increase neointimal formation. There are many instances where arterial injury needs repair and regeneration to avoid heart failure and death. For example in atherosclerosis, arterial aneurysms, and restenosis after balloon catheter stenosis. The goal of this study is to prevent these damaging effects by showing vasorin is involved and altered by exercise training. The second goal is to identify miRNAs that target vasorin and inhibit its production in cells of the aorta and coronary arteries. The third aim is to use anti-miR to the selected miRNAs that we show to be effective in inhibiting vasorin. Our goal is to establish a new therapeutic approach for arterial repair and regeneration. The study is novel in focusing on vasorin, miRNAs and scAAV delivery of vasorin or anti-miRNA to blood vessels to raise vasorin levels and for possible future gene therapy applications for vascular fibroproliferative disorders (AU)

Scientific publications

(4)

(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)

FERNANDES, TIAGO; BARRETTI, DIEGO LOPES; PHILLIPS, M. IAN; OLIVEIRA, EDILAMAR MENEZES. Exercise training prevents obesity-associated disorders: Role of miRNA-208a and MED13. Molecular and Cellular Endocrinology, v. 476, p. 148-154, NOV 15 2018. Web of Science Citations: 1.

FERNANDES, TIAGO; CASAES, LILIAN; SOCI, URSULA; SILVEIRA, ANDRE; GOMES, JOAO; BARRETTI, DIEGO; ROQUE, FERNANDA; OLIVEIRA, EDILAMAR. Exercise Training Restores the Cardiac Microrna-16 Levels Preventing Microvascular Rarefaction in Obese Zucker Rats. Obesity Facts, v. 11, n. 1, p. 15-24, 2018. Web of Science Citations: 3.

RENO SOCI, URSULA PAULA; FERNANDES, TIAGO; BARAUNA, VALERIO GARRONE; HASHIMOTO, NARA YUMI; ALVES MOTA, GLORIA DE FATIMA; ROSA, KALEIZU TEODORO; IRIGOYEN, MARIA CLAUDIA; PHILIPS, MICHAEL IAN; DE OLIVEIRA, EDILAMAR MENEZES. Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208. Clinical Science, v. 130, n. 22, p. 2005-2015, NOV 1 2016. Web of Science Citations: 12.

FERNANDES, TIAGO; BARAUNA, VALERIO G.; NEGRAO, CARLOS E.; PHILLIPS, M. IAN; OLIVEIRA, EDILAMAR M. Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 309, n. 4, p. H543-H552, AUG 15 2015. Web of Science Citations: 47.