The Role of Aryl Hydrocarbon Receptor in atherosclerotic plaque instability or vulnerability

• Grant number: 15/11742-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2015
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Pedro Afonso Barreto Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 16/09830-4 - Effects of aryl receptor activation on endothelial (dys)function, BE.EP.MS

Abstract

Atherosclerosis is a cardiovascular disease characterized by chronic inflammation in the subendothelial layer of the arteries. Local hemodynamic factors, such as shear stress and drag tension, play a key role in the development and progression of this disease. In the formation process of atherosclerotic plaques the accumulation of cellular remains and lipids lead to the formation of a necrotic core, which subsequently will compose the fibrous capsule, responsible for the plaque stabilization. Increased expression of metalloproteinase (MMP)-12, increased macrophages number and interleukin (IL)-8 levels are markers of vascular inflammation and atherosclerotic plaque formation. A reduction of vascular smooth muscle cells, increased number of macrophages, cytokines levels and MMPs activity are factors involved in the instability / vulnerability of the atherosclerotic plaque. The atherosclerotic plaque formation markers are increased by Hydrocarbon Receptor Aryl (AHR) activation. The AHR importantly contributes to the setting and clinical manifestations of cardiovascular diseases. Our hypothesis is that activation of the AHR increases macrophage, MMP-12 and release of cytokines during the atherosclerotic plaque formation, thus resulting in plaques with an unstable phenotype. The studies will be performed in control and apolipoprotein E deficient (ApoE -/-) mice, which will receive high-cholesterol diet and a device that allows vulnerable atherosclerotic plaque formation.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERREIRA, Pedro Afonso Barreto. Role of Aryl Hydrocarbon Receptors (AhR) in the development of atherosclerotic plaque vulnerability in apolipoprotein E knockout mice. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.