Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Nordic Bioscience, DK-2730 Herlev, Denmark.
Nordic Bioscience, DK-2730 Herlev, Denmark.
EBioMedicine. 2021 Jun;68:103391. doi: 10.1016/j.ebiom.2021.103391. Epub 2021 May 24.
The signalling peptide endotrophin is derived through proteolytic cleavage of the carboxyl-terminal during formation of type VI collagen. It is expressed by most descendants of the mesenchymal stem cells lineage, including adipocytes and fibroblasts, and have been proposed to be a central extracellular matrix hormone associated with several age-related diseases. We aimed to assess the association of endotrophin with chronic disease incidence and death in older women.
5,602 elderly Danish women from the observational, prospective cohort: The Prospective Epidemiological Risk Factor (PERF) study were included in the analysis which covered baseline (BL) and follow-up (FU) 14 years later. An elastic net was used to investigate the relative importance of 58 variables to serum endotrophin-levels. 20 chronic diseases were defined on the basis of clinical variables available along with diagnoses extracted from both the National Patient Register, the National Diabetes Register and the Danish Cancer Registry. The cross-sectional associations between endotrophin-levels and these 17 chronic age-related diseases were investigated using logistic regression and a set-analysis explored disease-combinations within multimorbidity. The association of endotrophin with mortality was assessed by Cox proportional hazard models.
Formation of type III collagen (PRO-C3), age and creatine-levels were the most influential variables of endotrophin-levels. Several chronic diseases were significantly associated with endotrophin-levels independent of age and BMI including chronic kidney disease (BL OR=3.7, p < 0.001; FU OR = 7.9 p < 0.001), diabetes (BL OR = 1.5, p = 0.0015, FU OR=1.6, p = 0.004) and peripheral arterial disease (BL OR = 1.3, p = 0.029; FU OR=2.4, p < 0.001). Lastly, endotrophin-levels were significantly rising with number of morbidities (p < 0.001) and a predictor of death after adjusting for age and BMI (BL HR=1.95; FU HR = 2.00).
Endotrophin was associated with death and increased with number of morbidities. Endotrophin may be a central hormone of fibroblast that warrant investigation and possible targeted intervention in several chronic diseases.
The funder of the PERF study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
信号肽内毒素通过形成 VI 型胶原过程中羧基末端的蛋白水解切割而产生。它由间充质干细胞谱系的大多数后代表达，包括脂肪细胞和成纤维细胞，并被提议作为与几种与年龄相关的疾病相关的中央细胞外基质激素。我们旨在评估内毒素与老年女性慢性疾病发病和死亡的关系。
5602 名丹麦老年女性来自观察性、前瞻性队列：前瞻性流行病学风险因素 (PERF) 研究被纳入分析，该研究涵盖了基线 (BL) 和 14 年后的随访 (FU)。弹性网络用于研究 58 个变量对内毒素水平的相对重要性。20 种慢性疾病是根据临床变量和从国家患者登记处、国家糖尿病登记处和丹麦癌症登记处提取的诊断定义的。使用逻辑回归研究内毒素水平与这些 17 种与年龄相关的慢性疾病之间的横断面关联，并通过集分析探索多疾病内的疾病组合。使用 Cox 比例风险模型评估内毒素与死亡率的关系。
III 型胶原形成 (PRO-C3)、年龄和肌酸水平是内毒素水平最具影响力的变量。一些慢性疾病与内毒素水平显著相关，独立于年龄和 BMI，包括慢性肾病 (BL OR=3.7，p<0.001；FU OR=7.9 p<0.001)、糖尿病 (BL OR=1.5，p=0.0015，FU OR=1.6，p=0.004) 和外周动脉疾病 (BL OR=1.3，p=0.029；FU OR=2.4，p<0.001)。最后，内毒素水平随着疾病数量的增加而显著升高 (p<0.001)，并且在调整年龄和 BMI 后是死亡的预测因子 (BL HR=1.95；FU HR=2.00)。
内毒素与死亡相关，并随着疾病数量的增加而增加。内毒素可能是成纤维细胞的中央激素，值得在几种慢性疾病中进行研究和可能的靶向干预。
PERF 研究的资助者在研究设计、数据收集、数据分析、数据解释或报告撰写方面没有任何作用。通讯作者可以完全访问研究中的所有数据，并对提交出版的决定拥有最终责任。
