New concepts for the fundamental role of LSD1 gene in cardiovascular and renal effects associated to salt dietary

• Grant number: 16/14696-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): January 01, 2017
• Effective date (End): April 30, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Joel Claudio Heimann
• Grantee: Isis Akemi Katayama
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Hypertension (HTN) is a well known risk factor for the development of cardiovascular and renal (CVR) diseases. The collaborating group recently proposed a novel contributor to the etiology of HTN mediated by salt: Lysine Specific Demethylase 1 (LSD1). The candidate worked with this group and demonstrated that in mice, the deficiency of LSD1 accelerates the increase of blood pressure (BP) levels and the development of microalbuminuria compared to the wild type (WT) animals. Interestingly, in the WT animals, the salt restriction prevented the cardiovascular effects observed in the group that was feed with a high salt diet (HSD), but the LSD1 heterozygous group (Het) this salt restriction diet was able only to blunt and delay the increase on BP. Furthermore, only the WT animals that receive salt restriction presented a normal renal resistance index and glomerular volume. There was no difference in the plasmatic aldosterone and in the plasma renin activity. This previous longitudinal study brings new and important concepts, however the mechanisms behind these phenotype need to be elucidated. The aim of the study is investigate the mechanisms involved on this genotype, which could explain the the early increased on BP and the microalbuminuria compared to the WT animals. The findings in mice of this group will support the animal and humans findings of the collaborator group, empowering the translational research. Thus, the LSD1 deficiency in mice and potentially in humans could be a biomarker of increase on BP and microalbuminuria development independent of the diet and the early adulthood could be an opportune time to initiate preventive measures to reduce future organ-target damage. Specifically, were used WT and LSD1 het male mice fed with high salt diet (1.6% sodium), normal salt diet (0.26% sodium) and low salt diet (0.03% sodium) for 12 monthsand the methods that will be use are: histology analyses of the renal tissue, ED-1, Angiotensin II and PCNA quantification (immunohistochemistry), evaluation of AT1 and AT2 receptors and gene and/or protein expressions of AT1, AT2 and MR receptors and CD68, MCP1, klotho, CaSR, FGF23, Sirt1 and LSD1 (AU)

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)

KATAYAMA, ISIS AKEMI; HUANG, YUEFEI; GARZA, AMANDA E.; BROOKS, DANIELLE L.; WILLIAMS, JONATHAN S.; NASCIMENTO, MARIANA M.; HEIMANN, JOEL C.; POJOGA, LUMINITA H.. Longitudinal changes in blood pressure are preceded by changes in albuminuria and accelerated by increasing dietary sodium intake. Experimental Gerontology, v. 173, p. 10-pg., 2023-02-06. (16/14696-5)