ABC | Volume 113, Nº6, December 2019

Original Article Barbosa et al Nrf2, NF- κ B and PPAR β / δ in CAD patients Arq Bras Cardiol. 2019; 113(6):1121-1127 Table 1 – Clinical profile and biochemical of the patients of the study Parameters Group without CAD (n = 12) CAD Group (n = 35) p value Men/women (n) 5/7 17/18 0.99 Age (years) 63.5 ± 11.5 62.4 ± 7.5 0.70 Hypertension (%) 91.7 97.1 0.81 Dyslipidemia (%) 75 74.2 0.67 Diabetes (%) 16.7 37.1 0.84 BMI (kg/m 2 ) 26.5 ± 6.2 28.9 ± 4.9 0.17 SBP (mmhg) 137.5 ± 23.0 138.0 ± 18.6 0.69 DBP (mmhg) 82.5 ± 9.6 82.8 ± 8.2 0.90 Total cholesterol (mg/dL) 200 ± 59.4 163.3 ± 46.7 0.03 LDL-cholesterol (mg/dL) 109.3 ± 53.3 79.9 ± 33.3 0.03 HDL-cholesterol (mg/dL) 65.1 ± 21.3 45.3 ± 9.9 0.002 Triglyceride (mg/dL) 128.2 ± 57.3 130.6 ± 71.8 0.79 Glucose (mg/dL) 115.2 ± 44.6 103.7 ± 36.4 0.13 CRP (mg/L) 0.6 (0.4-4.0) 2.0 (0.12-8.7) 0.25 CAD: coronary artery disease; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure CRP: C-reactive protein. Parametric data expressed as mean±SD and nonparametric data expressed with median, 15 th and 75 th quartiles. sample. A significance level of 5% was accepted. Statistical analyses were performed using the SPSS 19.0 software package (Chicago, IL, USA). Results In the CAD group, 82.8% presented abnormalities on myocardial perfusion scintigraphy (65.5% myocardial ischemia, 27.6% myocardial fibrosis, and 6.9% fibrosis and myocardial ischemia). Regarding the duration of disease, 71.4% were diagnosed with CAD from 1 to 5 years, 17.1% from 6 to 10 years and 11.5% from 10 to 15 years. According to the clinical history of patients with CAD, 54.2% performed some type of procedure before the study: 8.7% cardiac catheterization, 34.3% percutaneous transluminal coronary angioplasty, 5.7% percutaneous transluminal coronary angioplasty and cardiac catheterization and 5.7% percutaneous transluminal coronary angioplasty and coronary artery bypass grafting. Moreover, 62.8% of the CAD patients and 30.8% of the control group were smokers. Considering the use of medication, in the CAD group, 68.5% used β -adrenergic blockers, 17.4% angiotensin-converting enzyme inhibitor, 77.1% statins, 28.5% calcium channel blockers, 51.4% diuretic, 37.2% nitrate, 54.3% acetyl salicylic acid, 62.8% losartan potassium, 34.8% oral hypoglycemic agents and 11.43% insulin. In the control group, 53.8% used β -adrenergic blocker, 15.4% angiotensin-converting enzyme inhibitor, 46.2% statins, 30.8% calcium channel blocker, 53.8% diuretic, 7.7% nitrate, 61.5% acetyl salicylic acid, 69.2% losartan potassium, 38.5% oral hypoglycemic agents and 7.7% insulin. No statistical differences were found between groups related to the use of medication or smoking. Clinical profile and biochemical parameters are shown in Table 1. Also, the CAD group presented lower total cholesterol, LDL-cholesterol and HDL-cholesterol compared to the group without CAD (Table 1). No differences were found in the transcription factors Nrf2 and NF- κ B or in the NQO1 mRNA expression comparing the CAD group with the group without CAD. In contrast, the PPAR β / δ was more expressed in the CAD group (Table 2). We considered that the inclusion of diabetic patients did not interfere with the results. No correlations were found. Discussion Studies have evaluated systemic inflammation through PBMC gene expression. 26,27 The importance of studying PBMCs as a strategy to evaluate targets of inflammation-related metabolic pathways to explore CVD for a better understanding of the architecture of these diseases was emphasized. The hypothesis would be that the PBMCs could reflect inflammatory mechanisms in a more specific way compared to serum/plasma. 28 Thus, the present study investigates the transcription factors NF- κ B and Nrf2 and PPAR β / δ mRNA expression in PBMCs of CAD patients. CVD patients are usually exposed to inflammation and oxidative stress. Nrf2 protects the body against these conditions because it is related to the synthesis of antioxidant enzymes and is capable of antagonizing NF- κ B involved in inflammatory induction. Several studies have shown that NF- κ B plays an important role in the development of CVD. 29–31 It was demonstrated that ischemia rapidly induced NF- κ B activation in the myocardium of rats. 29 Wilson et al. 30 showed that NF- κ B was increased in the coronary atheromatous plaque in humans and its expression was predominantly associated with macrophages, foam cells and vascular smooth muscle cells. In addition, its expression was increased in acute coronary syndromes and associated with the intercellular adhesion molecule 1 1123