Impact of SET7 on pathological cardiac remodeling

• Grant number: 22/10060-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Gabriela Placoná Diniz
• Grantee: Guilherme Lunardon
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases are the main cause of death worldwide. In this sense, identifying the biological mechanisms involved in the development of structural and functional cardiac alterations is crucial for the development of new therapeutic strategies. Recent studies have revealed the influence of histone-modifying enzymes, such as methyltransferases, in the development of cardiac hypertrophy, fibrosis, and heart failure.The SET7 methyltransferase regulates the expression of several genes through the methylation of histones and also modulates the activity of non-histone proteins. A recent study from our laboratory showed that SET7 deletion in mice was able to attenuate isoproterenol-induced cardiac fibrosis. Furthermore, we identified that SET7 deletion prevented the reduction of systolic function induced by isoproterenol, and that this effect was accompanied by lower expression of genes related to fibrosis and cellular senescence. However, the biological mechanisms by which SET7 influences collagen deposition in the heart and cardiac function in response to isoproterenol remain unknown. Therefore, the aim of this study is to investigate the effect of SET7 inhibition in pathological cardiac remodeling through in vivo and in vitro studies.

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)

SILVA, TABATHA DE OLIVEIRA; LUNARDON, GUILHERME; LINO, CAROLINE A.; SILVA, AMANDA DE ALMEIDA; ZHANG, SHIJU; IRIGOYEN, MARIA CLAUDIA COSTA; LU, YAO WEI; MABLY, JOHN D.; BARRETO-CHAVES, MARIA LUIZA M.; WANG, DA-ZHI; et al. Senescent cell depletion alleviates obesity-related metabolic and cardiac disorders. MOLECULAR METABOLISM, v. 91, p. 15-pg., 2024-11-27. (22/10060-0, 20/13211-3, 20/14289-6, 23/03444-9, 23/02585-8)