Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605006, India.
Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605006, India.
Endocrine. 2022 Sep;77(3):461-468. doi: 10.1007/s12020-022-03141-5. Epub 2022 Jul 25.
Advanced glycation end products (AGEs) are responsible for the complications in type 2 diabetes mellitus (T2DM) patients by acting via its receptor (RAGE). The soluble form of RAGE (sRAGE) prevents the harmful effects of AGE-RAGE signalling. The sRAGE is produced either by alternate splicing (esRAGE) or proteolytic RAGE cleavage by a disintegrin and metalloproteinase 10 (ADAM10). Hence, the study aimed to compare the expression of ADAM10 in peripheral blood mononuclear cell (PBMC), serum sRAGE and esRAGE levels in T2DM patients with and without acute coronary syndrome (ACS).
Forty-five T2DM patients with ACS and 45 age, gender and duration of DM-matched T2DM patients without ACS were recruited. Serum sRAGE and esRAGE levels were measured by enzyme-linked immunosorbent assay. The expression of ADAM10 in PBMC was determined by quantitative reverse transcription-polymerase chain reaction.
The expression of ADAM10 in PBMC and serum sRAGE levels were significantly lower in T2DM patients with ACS than in T2DM patients without ACS (p < 0.001). Serum sRAGE levels and expression of ADAM10 in PBMC were positively correlated with each other and negatively correlated with markers of cardiac injury and glycaemic status (p < 0.05). Simple logistic regression showed that the models containing the expression of ADAM10 and serum sRAGE level could predict the ACS risk among T2DM patients. ROC analysis showed that both might be used for ACS diagnosis in T2DM patients.
Reduced expression of ADAM10 in PBMC might be responsible for lower serum sRAGE levels, predisposing T2DM patients to high ACS risk.
晚期糖基化终产物（AGEs）通过其受体（RAGE）发挥作用，导致 2 型糖尿病（T2DM）患者发生并发症。可溶性 RAGE（sRAGE）可防止 AGE-RAGE 信号的有害影响。sRAGE 是通过可变剪接（esRAGE）或解整合素金属蛋白酶 10（ADAM10）的蛋白水解 RAGE 裂解产生的。因此，本研究旨在比较 T2DM 合并急性冠状动脉综合征（ACS）患者和不合并 ACS 的 T2DM 患者外周血单个核细胞（PBMC）中 ADAM10 的表达、血清 sRAGE 和 esRAGE 水平。
招募了 45 例 T2DM 合并 ACS 患者和 45 例年龄、性别和糖尿病病程匹配的 T2DM 不合并 ACS 患者。采用酶联免疫吸附试验测定血清 sRAGE 和 esRAGE 水平。采用定量逆转录聚合酶链反应测定 PBMC 中 ADAM10 的表达。
T2DM 合并 ACS 患者 PBMC 中 ADAM10 的表达和血清 sRAGE 水平明显低于 T2DM 不合并 ACS 患者（p<0.001）。血清 sRAGE 水平与 PBMC 中 ADAM10 的表达呈正相关，与心脏损伤和血糖状态标志物呈负相关（p<0.05）。简单逻辑回归显示，包含 ADAM10 表达和血清 sRAGE 水平的模型可预测 T2DM 患者 ACS 风险。ROC 分析表明，两者均可用于 T2DM 患者 ACS 的诊断。
PBMC 中 ADAM10 的表达降低可能导致血清 sRAGE 水平降低，使 T2DM 患者易发生 ACS 风险。
