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低密度脂蛋白胆固醇/高密度脂蛋白胆固醇比值及NADPH氧化酶2衍生的氧化应激作为病态肥胖受试者微血管内皮功能的主要决定因素

LDL-c/HDL-c Ratio and NADPH-Oxidase-2-Derived Oxidative Stress as Main Determinants of Microvascular Endothelial Function in Morbidly Obese Subjects.

作者信息

Santos Jorge, La Fuente José M, Fernández Argentina, Ruano Paula, Angulo Javier

机构信息

Unidade de Cirurgia Esofagogástrica e Tratamento Cirúrgico de Obesidade, Centro Hospitalar e Universitário de Santo António (CHUdSA), 4099-001 Porto, Portugal.

Serviço de Urologia, Centro Hospitalar e Universitário de Santo António (CHUdSA), 4099-001 Porto, Portugal.

出版信息

Antioxidants (Basel). 2024 Sep 20;13(9):1139. doi: 10.3390/antiox13091139.

Abstract

The identification of obese subjects at higher risk for cardiovascular disease (CVD) is required. We aimed to characterize determinants of endothelial dysfunction, the initial step to CVD, in small omental arteries of visceral fat from obese subjects. The influences of analytical parameters and vascular oxidative stress mediated by NADPH-oxidase-2 (NOX2) on endothelial function were determined. Specimens were obtained from 51 obese subjects undergoing bariatric surgery and 14 non-obese subjects undergoing abdominal surgery. Obese subjects displayed reduced endothelial vasodilation to bradykinin (BK). Endothelial vasodilation (pEC for BK) among obese subjects was significantly and negatively associated with low-density lipoprotein cholesterol (LDL-c)/high-density lipoprotein cholesterol (HDL-c) ratio (r = -0.510, = 0.0001) in both women and men, while other metabolic parameters and comorbidities failed to predict endothelial function. The vascular expression of NOX2 was upregulated in obese subjects and was related to decreased endothelial vasodilation (r = -0.529, = 0.0006, = 38) and increased oxidative stress (r = 0.783, = 0.0044, = 11) in arterial segments. High LDL-c/HDL-c (>2) and high NOX2 (above median) were independently associated with reduced endothelial function, but the presence of both conditions was related to a further impairment. Concomitant elevated LDL-c/HDL-c ratio and high vascular expression of NOX2 would exacerbate endothelial impairment in obesity and could reveal a deleterious profile for cardiovascular outcomes among obese subjects.

摘要

需要识别出心血管疾病(CVD)风险较高的肥胖受试者。我们旨在描述肥胖受试者内脏脂肪小网膜动脉中内皮功能障碍(CVD的起始步骤)的决定因素。确定了分析参数和由NADPH氧化酶-2(NOX2)介导的血管氧化应激对内皮功能的影响。样本取自51例接受减肥手术的肥胖受试者和14例接受腹部手术的非肥胖受试者。肥胖受试者对缓激肽(BK)的内皮血管舒张功能降低。在肥胖受试者中,内皮血管舒张功能(BK的pEC)在男性和女性中均与低密度脂蛋白胆固醇(LDL-c)/高密度脂蛋白胆固醇(HDL-c)比值显著负相关(r = -0.510,P = 0.0001),而其他代谢参数和合并症无法预测内皮功能。肥胖受试者中NOX2的血管表达上调,且与动脉节段中内皮血管舒张功能降低(r = -0.529,P = 0.0006,n = 38)和氧化应激增加(r = 0.783,P = 0.0044,n = 11)相关。高LDL-c/HDL-c(>2)和高NOX2(高于中位数)与内皮功能降低独立相关,但两种情况同时存在与进一步的损害有关。LDL-c/HDL-c比值升高和NOX2的血管高表达同时存在会加重肥胖患者的内皮损伤,并可能揭示肥胖受试者心血管结局的有害特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ef8/11444145/0a25f75a0e37/antioxidants-13-01139-g001.jpg

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