Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure Pricila Rodrigues Gonçalves, Lisandra Duarte Nascimento, Raquel Fernanda Gerlach, Keuri Eleutério Rodrigues, Alejandro Ferraz Prado Pharmaceuticals, 2022 Heart failure (HF) is an acute or chronic clinical syndrome that results in a decrease in cardiac output and an increase in intracardiac pressure at rest or upon exertion. The pathophysiology of HF is heterogeneous and results from an initial harmful event in the heart that promotes neurohormonal changes such as autonomic dysfunction and activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and inflammation. Cardiac remodeling occurs, which is associated with degradation and disorganized synthesis of extracellular matrix (ECM) components that are controlled by ECM metalloproteinases (MMPs). MMP-2 is part of this group of proteases, which are classified as gelatinases and are constituents of the heart. MMP-2 is considered a biomarker of patients with HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The role of MMP-2 in the development of cardiac injury and dysfunction has clearly been demonstrated in animal models of cardiac ischemia, transgenic models that overexpress MMP-2, and knockout models for this protease. New research to minimize cardiac structural and functional alterations using non-selective and selective inhibitors for MMP-2 demonstrates that this protease could be used as a possible pharmacological target in the treatment of HF.
Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE-⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity Keuri E. Rodrigues, Aline Azevedo, Pricila R. Gonçalves, Maria H. B. Pontes, Gustavo M. Alves, et al. International Journal of Molecular Sciences, 2022 Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE-⁄- and ovariectomized mice (OVX). Female ApoE-⁄--knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE-⁄-/OVX vehicle and ApoE-⁄-/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE-⁄-/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE-⁄-/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE-⁄-/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression.
Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: Role of SIRT1 Bruno Alexandre Quadros Gomes, João Paulo Bastos Silva, Camila Fernanda Rodrigues Romeiro, Sávio Monteiro dos Santos, Caroline Azulay Rodrigues, et al. Oxidative Medicine and Cellular Longevity, 2018 Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence of β‐amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβ peptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti‐inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβ peptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator‐1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti‐inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti‐inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti‐inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.
RECENT SCHOLAR PUBLICATIONS
BmooMPα-I ameliorates aortic fibrosis and hypertrophy in 2K1C hypertensive rats by reducing matrix metalloproteinase-2 activity WF Dias, JEC Estrada, SCP Silva, PR Gonçalves, AM Lima, M Hamoy, ... Toxicon, 109120 , 2026 2026.0
Matrix metalloproteinase 2 as a pharmacological target in heart failure PR Gonçalves, LD Nascimento, RF Gerlach, KE Rodrigues, AF Prado Pharmaceuticals 15 (8), 920 , 2022 2022.0 Citations: 69
Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE -⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity KE Rodrigues, A Azevedo, PR Gonçalves, MHB Pontes, GM Alves, ... International Journal of Molecular Sciences 23 (5), 2532 , 2022 2022.0 Citations: 7
Efeito protetor do ácido alfa lipóico sobre a lesão hepática, induzida por dapsona em modelo animal JT Sakai 2018.0
Neuroprotective Mechanisms of Resveratrol in Alzheimer's Disease: Role of SIRT1, Oxidative Medicine and Cellular Longevity (2018) BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... Artn , 2018 2018.0 Citations: 8
Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: role of SIRT1 BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... Oxidative medicine and cellular longevity 2018 (1), 8152373 , 2018 2018.0 Citations: 454
Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: role of SIRT1. Oxid Med Cell Longev 2018: 8152373 BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... 2018.0 Citations: 17
OXID MED CELL LONGEV BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... DOI 10.1155/2016/8695716 , 2016 2016.0 Citations: 5
Exploiting the IEEE 1149.1 standard for software reliability evaluation in space applications M Zenha-Rela, JC Cunha, LE Santos, M Gameiro, P Gonçalves, GR Alves, ... 2006.0 Citations: 8
AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE DE N-ACETILCISTEÍNA IN VITRO: POTENCIAL TRATAMENTO ADJUVANTE NA POLIQUIMIOTERAPIA DA HANSENÍASE CA Rodrigues, SM dos Santos, ARQ Gomes, BAQ Gomes, PR Gonçalves, ...
EFEITOS DO ALFA-TOCOFEROL NA A METEMOGLOBINA E ESTRESSE OXIDATIVO INDUZIDOS PELA DAPSONA-HIDROXILAMINA IN VITRO PR Gonçalves, SM dos Santos, BAQ Gomes, JT Sakai, C Azulay
MOST CITED SCHOLAR PUBLICATIONS
Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: role of SIRT1 BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... Oxidative medicine and cellular longevity 2018 (1), 8152373 , 2018 2018.0 Citations: 454
Matrix metalloproteinase 2 as a pharmacological target in heart failure PR Gonçalves, LD Nascimento, RF Gerlach, KE Rodrigues, AF Prado Pharmaceuticals 15 (8), 920 , 2022 2022.0 Citations: 69
Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: role of SIRT1. Oxid Med Cell Longev 2018: 8152373 BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... 2018.0 Citations: 17
Neuroprotective Mechanisms of Resveratrol in Alzheimer's Disease: Role of SIRT1, Oxidative Medicine and Cellular Longevity (2018) BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... Artn , 2018 2018.0 Citations: 8
Exploiting the IEEE 1149.1 standard for software reliability evaluation in space applications M Zenha-Rela, JC Cunha, LE Santos, M Gameiro, P Gonçalves, GR Alves, ... 2006.0 Citations: 8
Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE -⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity KE Rodrigues, A Azevedo, PR Gonçalves, MHB Pontes, GM Alves, ... International Journal of Molecular Sciences 23 (5), 2532 , 2022 2022.0 Citations: 7
OXID MED CELL LONGEV BAQ Gomes, JPB Silva, CFR Romeiro, SM Dos Santos, CA Rodrigues, ... DOI 10.1155/2016/8695716 , 2016 2016.0 Citations: 5
BmooMPα-I ameliorates aortic fibrosis and hypertrophy in 2K1C hypertensive rats by reducing matrix metalloproteinase-2 activity WF Dias, JEC Estrada, SCP Silva, PR Gonçalves, AM Lima, M Hamoy, ... Toxicon, 109120 , 2026 2026.0
Efeito protetor do ácido alfa lipóico sobre a lesão hepática, induzida por dapsona em modelo animal JT Sakai 2018.0
AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE DE N-ACETILCISTEÍNA IN VITRO: POTENCIAL TRATAMENTO ADJUVANTE NA POLIQUIMIOTERAPIA DA HANSENÍASE CA Rodrigues, SM dos Santos, ARQ Gomes, BAQ Gomes, PR Gonçalves, ...
EFEITOS DO ALFA-TOCOFEROL NA A METEMOGLOBINA E ESTRESSE OXIDATIVO INDUZIDOS PELA DAPSONA-HIDROXILAMINA IN VITRO PR Gonçalves, SM dos Santos, BAQ Gomes, JT Sakai, C Azulay
