Girona Josefa, Rodríguez-Borjabad Cèlia, Ibarretxe Daiana, Vallvé Joan-Carles, Ferré Raimon, Heras Mercedes, Rodríguez-Calvo Ricardo, Guaita-Esteruelas Sandra, Martínez-Micaelo Neus, Plana Núria, Masana Lluís
Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, 43201 Reus, Spain.
Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain.
J Clin Med. 2019 Oct 26;8(11):1793. doi: 10.3390/jcm8111793.
Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese individuals.
To investigate the role of the GRP78/BiP level as a metabolic and vascular disease biomarker in patients with type 2 diabetes (DM), obesity and metabolic syndrome (MS).
Four hundred and five patients were recruited, of whom 52.5% were obese, 72.8% had DM, and 78.6% had MS. The intimae media thickness (cIMT) was assessed by ultrasonography. The plasma GRP78/BiP concentration was determined, and its association with metabolic and vascular parameters was assessed. Circulating GRP78/BiP was also prospectively measured in 30 DM patients before and after fenofibrate/niacin treatment and 30 healthy controls.
In the cross-sectional study, the GRP78/BiP level was significantly higher in the patients with obesity, DM, and MS. Age-, gender- and BMI-adjusted GRP78/BiP was directly associated with LDL-cholesterol, non-HDL-cholesterol, triglycerides, apoB, and cIMT. GRP78/BiP was positively associated to carotid plaque presence in the adjusted model, irrespective of obesity, DM and MS. In the prospective study, nicotinic acid treatment produced a significant reduction in the GRP78/BiP levels that was not observed with fenofibrate.
GRP78/BiP plasma concentrations are increased in patients with both metabolic derangements and subclinical atherosclerosis. GRP78/BiP could be a useful marker of metabolic and cardiovascular risk.
葡萄糖调节蛋白78/结合免疫球蛋白蛋白（GRP78/BiP）是一种与内质网应激相关的蛋白，在组织水平上会因代谢改变（如缺氧或葡萄糖剥夺）而上调，并且在肥胖个体的脂肪组织中高表达。
研究GRP78/BiP水平作为2型糖尿病（DM）、肥胖症和代谢综合征（MS）患者代谢和血管疾病生物标志物的作用。
招募了405例患者，其中52.5%为肥胖患者，72.8%患有DM，78.6%患有MS。通过超声检查评估内膜中层厚度（cIMT）。测定血浆GRP78/BiP浓度，并评估其与代谢和血管参数的关联。还对30例DM患者在非诺贝特/烟酸治疗前后以及30例健康对照者进行了循环GRP78/BiP的前瞻性测量。
在横断面研究中，肥胖、DM和MS患者的GRP78/BiP水平显著更高。经年龄、性别和体重指数调整后的GRP78/BiP与低密度脂蛋白胆固醇、非高密度脂蛋白胆固醇甘油三酯、载脂蛋白B和cIMT直接相关。在调整模型中，无论肥胖、DM和MS如何，GRP78/BiP与颈动脉斑块的存在呈正相关。在前瞻性研究中，烟酸治疗使GRP78/BiP水平显著降低，而非诺贝特治疗未观察到这种情况。
代谢紊乱和亚临床动脉粥样硬化患者的血浆GRP78/BiP浓度升高。GRP78/BiP可能是代谢和心血管风险的有用标志物。
