Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Int J Mol Sci. 2022 Oct 31;23(21):13266. doi: 10.3390/ijms232113266.
Coronary artery spasm (CAS) plays an important role in the pathogenesis of many ischemic heart entities; however, there are no established diagnostic biomarkers for CAS in clinical and forensic settings. This present study aimed to identify such serum biomarkers by establishing a rabbit CAS provocation model and integrating quantitative serum proteomics, parallel reaction monitoring/mass spectrometry-based targeted proteomics, and partial least-squares discriminant analysis (PLS-DA). Our results suggested that SELENBP1 and VCL were potential candidate biomarkers for CAS. In independent clinical samples, SELENBP1 and VCL were validated to be significantly lower in serum but not blood cells from CAS patients, with the reasons for this possibly due to the decreased secretion from cardiomyocytes. The areas under the curve of the receiver operating characteristics (ROC) analysis were 0.9384 for SELENBP1 and 0.9180 for VCL when diagnosing CAS. The CAS risk decreased by 32.3% and 53.6% for every 10 unit increases in the serum SELENBP1 and VCL, respectively. In forensic samples, serum SELENBP1 alone diagnosed CAS-induced deaths at a sensitivity of 100.0% and specificity of 72.73%, and its combination with VCL yielded a diagnostic specificity of 100.0%, which was superior to the traditional biomarkers of cTnI and CK-MB. Therefore, serum SELENBP1 and VCL could be effective biomarkers for both the clinical and forensic diagnosis of CAS.
冠状动脉痉挛（CAS）在许多缺血性心脏实体的发病机制中起着重要作用；然而，在临床和法医学环境中，没有用于 CAS 的既定诊断生物标志物。本研究旨在通过建立兔 CAS 诱发模型，并结合定量血清蛋白质组学、平行反应监测/基于质谱的靶向蛋白质组学和偏最小二乘判别分析（PLS-DA），来确定这种血清生物标志物。我们的结果表明，SELENBP1 和 VCL 是 CAS 的潜在候选生物标志物。在独立的临床样本中，SELENBP1 和 VCL 在 CAS 患者的血清中而非血细胞中被验证为显著降低，其原因可能是心肌细胞分泌减少。SELENBP1 和 VCL 诊断 CAS 的受试者工作特征（ROC）曲线下面积分别为 0.9384 和 0.9180。血清 SELENBP1 和 VCL 每增加 10 个单位，CAS 的风险分别降低 32.3%和 53.6%。在法医样本中，血清 SELENBP1 单独用于诊断 CAS 诱导的死亡，其灵敏度为 100.0%，特异性为 72.73%，而与 VCL 联合使用时，特异性为 100.0%，优于传统的 cTnI 和 CK-MB 生物标志物。因此，血清 SELENBP1 和 VCL 可能是 CAS 的临床和法医诊断的有效生物标志物。
