Increase in the complement system and reduction in T regulatory cells may increase the activity of matrix metalloproteinase(MMP)-2 and arterial remodelling in hypertension

• Grant number: 23/04177-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2023
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Michele Mazzaron de Castro
• Grantee: Luan Victor Resque Ramos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Hypertension is associated with inflammation and immune response and then the hypertensive patients have higher plasma concentrations of pro-inflammatory cytokines. The generation of reactive oxygen species (ROS), the expression and release of cytokines and chemokines, and the infiltration of immune cells in the kidneys and arteries is characteristic of hypertension. Oxidative stress may participate in the regulation of the immune response in hypertension through the activation of the complement system and regulation of regulatory T cells (Tregs). The complement system, in turn, physiologically decreases the expression and function of circulating Tregs in vivo, so that, increased complement results in inhibition of the suppressive capacity of this cells and in oxidative stress. Moreover, oxidative stress is able to increase the activity of MMP-2, an important protease for arterial remodelling in animal models of hypertension, while the complement system increases the expression of MMP-2 in an animal model of aneurysm. Knowing that increased complement system occurs in hypertension, the hypothesis is that increased complement system C3a contributes to reduce Tregs and increase MMP-2 activity, which then leads to arterial remodelling in hypertension. Hypertension will be induced in C57BL/6 mice by the infusion of angiotensin II by osmotic mini-pumps, and they will be treated with C3aR antagonist, SB290157 (or vehicle). Blood pressure will be evaluated by tail-cuff plethysmography and the expression of Foxp3, C3a, C3aR, MMP-2, IL-6 and IL-10 will be determined by Western Blot, Elisa and RT-PCR; MMP-2 activity will be determined by gel and in situ zymography and oxidative stress by DHE; arterial remodelling analysis will be evaluated by H&E staining; CD4, CD25 and CD127 labeling will be used in the flow cytometry.

Academic Publications

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

RAMOS, Luan Victor Resque. Increased complement system and reduced regulatory T cells may increase the activity of matrix metalloproteinase (MMP)-2 and arterial remodeling in hypertension. 2024. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.