Januszewski Andrzej S, Watson Chris J, O'Neill Vikki, McDonald Kenneth, Ledwidge Mark, Robson Tracy, Jenkins Alicia J, Keech Anthony C, McClements Lana
NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, UK.
Sci Rep. 2020 Dec 10;10(1):21655. doi: 10.1038/s41598-020-78676-6.
Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non-diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism.
2型糖尿病（T2D）与心血管疾病（CVD）风险增加相关。由于血管生成紊乱和内皮功能障碍在T2D和CVD中起重要作用，我们旨在研究一种新型抗血管生成蛋白FK506结合蛋白样蛋白（FKBPL）与这些疾病之间的关联。采用酶联免疫吸附测定法（ELISA）对353名成年人进行横断面血浆FKBPL定量分析，这些成年人包括234名T2D患者和119名有/无CVD的非糖尿病患者，按年龄、体重指数（BMI）和性别进行匹配。调整CVD状态后，T2D患者的FKBPL水平（校正均值：2.03 ng/ml±0.90标准差）高于非糖尿病患者（校正均值：1.79 ng/ml±0.89标准差，p = 0.02）。在T2D患者中，FKBPL与空腹血糖、糖化血红蛋白（HbA1c）和舒张压（DBP）呈负相关，与年龄、已知糖尿病病程、腰臀比、尿白蛋白/肌酐比值（ACR）和空腹C肽呈正相关。存在CVD时，血浆FKBPL浓度升高，但仅在非糖尿病组中如此（CVD组：2.02 ng/ml±0.75标准差，无CVD组：1.68 ng/ml±0.79标准差，p = 0.02）。在非糖尿病患者中，FKBPL与已确立的CVD生物标志物B型利钠肽（BNP）以及舒张功能障碍的超声心动图参数呈正相关。除年龄、性别、总胆固醇和收缩压（SBP）外，FKBPL是非糖尿病组CVD的一个决定因素。FKBPL在无糖尿病的情况下可能是CVD中一种有用的抗血管生成生物标志物，并且可能代表一种新的CVD机制。
