ABC | Volume 113, Nº6, December 2019

Original Article Nrf2, NF-κB and PPARβ/δ mRNA Expression Profile in Patients with Coronary Artery Disease Jaqueline Ermida Barbosa, Milena Barcza Stockler-Pinto, Beatriz Oliveira da Cruz , Ana Carla Tavares da Silva , Juliana Saraiva Anjos, Claudio Tinoco Mesquit a, D enise Mafra, Ludmila F. M. F. Cardoz o Universidade Federal Fluminense - Programa de Pós-Graduação em Ciências Cardiovasculares, Niterói, RJ – Brazil Mailing Address: Ludmila F. M. F. Cardozo • Universidade Federal Fluminense - Hospital Universitário Antônio Pedro - Rua Marques do Paraná, 303, 4º andar - prédio da emergência. Postal Code 24033‑900, Niterói RJ – Brazil E-mail: ludmila.cardozo@gmail.com Manuscript received October 17, 2018, revised manuscript February 07, 2019, accepted February 13, 2019 DOI: 10.5935/abc.20190125 Abstract Background: Oxidative stress and inflammation are present in coronary artery disease (CAD) and are linked to the activation of the transcription nuclear factor kappa B (NF- κ B). To attenuate these complications, transcription factors like nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor- β / δ (PPAR β / δ ) can be activated to inhibit NF- κ B. However, the available data on expression of NF- κ B, Nrf2 and PPAR β / δ in CAD patients are limited. Objective: To evaluate the expression of the transcription factors NF- κ B and Nrf2 and PPAR / in CAD patients. Methods: Thirty-five patients (17 men, mean age 62.4  ±  7.55 years) with CAD and twelve patients (5 men, mean age 63.50  ±  11.46 years) without CAD were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and processed for mRNA expression of Nrf2, NF- κ B, NADPH: quinone oxidoreductase 1 (NQO1) and PPAR β / δ mRNAs using quantitative real-time polymerase chain reaction (qPCR). p < 0.05 was considered statistically significant. Results: There was no difference in the mRNA expressions of Nrf2 (1.35 ± 0.57), NF- κ B (1.08 ± 0.50) or in the antioxidant enzyme NQO1 (1.05 ± 0.88) in the CAD group compared to the group without CAD (1.16 ± 0.76, 0.95 ± 0.33, 0.81 ± 0.55, respectively). However, PPAR β / δ was highest expressed in the CAD group (1.17  ± 0.86 vs. 0.56  ± 0.34, p = 0.008). Conclusion: The main finding of this study was the PPAR β / δ being more expressed in the PBMC of patients with CAD compared to the control group, whereas no differences were observed in Nrf2 or NF- κ B mRNA expressions. (Arq Bras Cardiol. 2019; 113(6):1121-1127) Keywords: Coronary Artery Disease; Oxidative Stress; Inflammation; Obesity; Hypertension; Dyslipidemias; Risk Factors/prevalence; Myocardial Infarction; Heart Failure. Introduction Of all cardiovascular diseases (CVD), coronary artery disease (CAD) is the leading cause of death and high expenditure on medical assistance in the world, and is typically a chronic disease with progression over years or decades. 1–3 CAD, also known as coronary arteriosclerotic heart disease or coronary heart disease, is characterized by narrowing of the arteries in the heart that supply blood, oxygen, and nutrients to the cardiac tissue. 4 Although there has been a steady decline in the incidence of CVD in recent years, the prevalence of CVD risk factors (hypertension, high cholesterol and obesity) has been increasing. Smoking, obesity, high blood pressure (BP), high total cholesterol and low-density lipoprotein, low high‑density lipoprotein, diabetes and advanced age are the main risk factors for CVD 5,6 and are directly related to endothelial dysfunction with low bioavailability of nitric oxide, causing vasoconstriction, oxidative stress and inflammation. 7,8 Oxidative stress is present in both etiology and progression of myocardial infarction, congestive heart failure, atherosclerosis and hypertension. 9 Oxidative stress arises when there is an imbalance between the reactive oxygen species (ROS) production and the capacity of the antioxidant defense systems of the body, 10 while inflammation is a biological response to oxidative stress where the cell starts producing proteins, enzymes and other compounds to restore homeostasis. 11 Oxidative stress is responsible for inflammation by several mechanisms, one of which is the direct activation of the nuclear transcription factor kappa B (NF- κ B) by the ROS. NF- κ B regulates the transcription of several genes encoding proinflammatory cytokines, chemokines and adhesion molecules of leukocytes. In this direction, it is important to evaluate factors that attenuate both inflammation and oxidative stress. Nuclear factor erythroid 2-related to factor 2 (Nrf2) has been associated with cytoprotective effects and its accumulation leads to an increase in the transcription of antioxidant response elements (ARE)-regulated genes encoding antioxidant and phase 2 detoxifying enzymes and can be considered a protective factor against both oxidative stress and inflammation. 12-14 Under basal conditions, Nrf2 is inactive in the cytoplasm 1121