EVALUATION OF THE EPIGENETIC EFFECTS OF ATORVASTATIN ON THE REGULATION OF EXPRESSION OF GENES RELATED TO NITRIC OXIDE IN EXPERIMENTAL HYPERTENSION MODEL

• Grant number: 18/18312-2
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2019 - January 31, 2022
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Riccardo Lacchini
• Grantee: Riccardo Lacchini
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Nitric oxide (NO) is the main factor responsible for vascular relaxation. Reduction of NO production by reduced expression or activity of endothelial nitric oxide synthase (eNOS) or reduced soluble guanylate cyclase (sGC) activity may lead to cardiovascular disease. The NOS3 gene has its expression strongly restricted to vascular endothelial cells through DNA methylation. It has been experimentally demonstrated that changes in NOS3 methylation may predispose to cardiovascular disease. Atorvastatin has been studied in the context of cancer as a demethylation agent. Here, our objective is to investigate these hypotheses: 1) Will the temporal course of hypertension change the epigenetic regulation of nitric oxide and matrix metalloproteinases - related genes in endothelial and smooth muscle cells? 2) Will the treatment of hypomethylation (5'aza-deoxycytidine) alter the beneficial effects of Atorvastatin in a renovascular hypertension model? Wistar rats will be used in which hypertension will be induced by 2K1C surgery (2 kidneys 1 clip). Aortic rings of chronically treated animals will be evaluated for vascular reactivity using dose-dependent curves and presence / absence of antagonists. Approaches with generic and specific techniques will be used to quantify DNA methylation of aortic smooth muscle and endothelial cells. The genes evaluated for epigenetic changes following chronic treatments will be NOS3, MMP-2 and MMP-9. (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)

OLIVEIRA-PAULA, GUSTAVO H.; PEREIRA, SHERLIANE C.; TANUS-SANTOS, JOSE E.; LACCHINI, RICCARDO. Pharmacogenomics And Hypertension: Current Insights. PHARMACOGENOMICS & PERSONALIZED MEDICINE, v. 12, p. 341-359, 2019. (18/18312-2)

OLIVEIRA-PAULA, GUSTAVO H.; COELI-LACCHINI, FERNANDA BORCHERS; FEREZIN, LETICIA PERTICARRARA; FERREIRA, GRAZIELE C.; PINHEIRO, LUCAS C.; PAULA-GARCIA, WAYNICE N.; GARCIA, LUIS V.; TANUS-SANTOS, JOSE E.; LACCHINI, RICCARDO. Arginase II polymorphisms modify the hypotensive responses to propofol by affecting nitric oxide bioavailability. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, v. 77, n. 6, JAN 2021. (18/18312-2)