Pérez-Belmonte Luis M, Moreno-Santos Inmaculada, Gómez-Doblas Juan J, García-Pinilla José M, Morcillo-Hidalgo Luis, Garrido-Sánchez Lourdes, Santiago-Fernández Concepción, Crespo-Leiro María G, Carrasco-Chinchilla Fernando, Sánchez-Fernández Pedro L, de Teresa-Galván Eduardo, Jiménez-Navarro Manuel
Unidad de Gestión Clínica Área del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), CIBERCV Enfermedades Cardiovasculares, Málaga, Spain.
Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Spain.
Int J Med Sci. 2017 Jul 20;14(9):891-895. doi: 10.7150/ijms.19854. eCollection 2017.
Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.
已有研究提出心外膜脂肪组织参与心力衰竭的发病机制。我们研究的目的是评估心力衰竭患者心外膜脂肪组织中产热基因（解偶联蛋白1（UCP1）、过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1α）和PR结构域缺失16（PRDM16））的表达情况，并根据左心室射血分数（降低或保留）确定差异。在我们研究的75例患者中，42.7%（n = 32）的患者左心室射血分数降低。左心室射血分数降低的患者，心外膜脂肪组织中的UCP1、PGC1α和PRDM16 mRNA显著较低。多元回归分析显示，年龄、男性性别、体重指数、肥胖、2型糖尿病、高血压和冠状动脉疾病以及左心室射血分数与UCP1、PGC1α和PRDM16 mRNA的表达水平相关。心外膜脂肪组织中产热基因的表达（UCP1：OR 0.617，95%CI 0.103 - 0.989，p = 0.042；PGC1α：OR 0.416，95%CI 0.171 - 0.912，p = 0.031；PRDM16：OR 0.643，95%CI 0.116 - 0.997，p = 0.044）被证明是左心室射血分数降低的心力衰竭存在的保护因素，而年龄（OR 1.643，95%CI 1.001 - 3.143，p = 0.026）、冠状动脉疾病的存在（OR 6.743，95%CI 1.932 - 15.301，p < 0.001）和2型糖尿病（OR 4.031，95%CI 1.099 - 7.231，p < 0.001）被认为是危险因素。产热基因的充分表达已被证明可能是射血分数降低的心力衰竭的保护因素，这表明功能性心外膜脂肪组织棕色样特征的丧失会对心脏代谢产生有害影响。产热基因可能代表心力衰竭未来新的治疗靶点。
