Department of Biochemistry and Molecular Biology The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Department of Surgery The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2020 Aug 5;15(8):e0234539. doi: 10.1371/journal.pone.0234539. eCollection 2020.
Diabetes Mellitus (DM) accelerates coronary artery disease (CAD) and atherosclerosis, the causes of most heart attacks. The biomolecules involved in these inter-related disease processes are not well understood. This study analyzes biomolecules in the sera of patients with CAD, with and without type (T) 2DM, who are about to undergo coronary artery bypass graft (CABG) surgery. The goal is to develop methodology to help identify and monitor CAD patients with and without T2DM, in order to better understand these phenotypes and to glean relationships through analysis of serum biomolecules. Aorta, fat, muscle, and vein tissues from CAD T2DM patients display diabetic-related histologic changes (e.g., lipid accumulation, fibrosis, loss of cellularity) when compared to non-diabetic CAD patients. The patient discriminatory methodology utilized is serum biomolecule mass profiling. This mass spectrometry (MS) approach is able to distinguish the sera of a group of CAD patients from controls (p value 10-15), with the CAD group containing both T2DM and non-diabetic patients. This result indicates the T2DM phenotype does not interfere appreciably with the CAD determination versus control individuals. Sera from a group of T2DM CAD patients however are distinguishable from non-T2DM CAD patients (p value 10-8), indicating it may be possible to examine the T2DM phenotype within the CAD disease state with this MS methodology. The same serum samples used in the CAD T2DM versus non-T2DM binary group comparison were subjected to MS/MS peptide structure analysis to help identify potential biochemical and phenotypic changes associated with CAD and T2DM. Such peptide/protein identifications could lead to improved understanding of underlying mechanisms, additional biomarkers for discriminating and monitoring these disease conditions, and potential therapeutic targets. Bioinformatics/systems biology analysis of the peptide/protein changes associated with CAD and T2DM suggested cell pathways/systems affected include atherosclerosis, DM, fibrosis, lipogenesis, loss of cellularity (apoptosis), and inflammation.
糖尿病（DM）可加速冠状动脉疾病（CAD）和动脉粥样硬化，这是大多数心脏病发作的原因。这些相互关联的疾病过程中涉及的生物分子还没有被很好地理解。本研究分析了即将接受冠状动脉旁路移植（CABG）手术的 CAD 患者的血清中的生物分子，包括有和没有 2 型糖尿病（T2DM）的患者。目的是开发一种方法来帮助识别和监测有和没有 T2DM 的 CAD 患者，以便更好地了解这些表型，并通过分析血清生物分子来获得关系。与非糖尿病 CAD 患者相比，CAD T2DM 患者的主动脉、脂肪、肌肉和静脉组织显示出与糖尿病相关的组织学变化（例如，脂质积累、纤维化、细胞减少）。所利用的患者鉴别方法是血清生物分子质量分析。这种质谱（MS）方法能够区分一组 CAD 患者与对照组（p 值为 10-15）的血清，其中 CAD 组包含 T2DM 和非糖尿病患者。这一结果表明，T2DM 表型与对照个体相比，不会明显干扰 CAD 的确定。然而，一组 T2DM CAD 患者的血清与非 T2DM CAD 患者是可区分的（p 值为 10-8），这表明用这种 MS 方法可能有可能在 CAD 疾病状态下检查 T2DM 表型。用于 CAD T2DM 与非 T2DM 二项组比较的相同血清样本还进行了 MS/MS 肽结构分析，以帮助鉴定与 CAD 和 T2DM 相关的潜在生化和表型变化。这种肽/蛋白质鉴定可能会导致对潜在机制的深入了解、区分和监测这些疾病状况的额外生物标志物，以及潜在的治疗靶点。与 CAD 和 T2DM 相关的肽/蛋白质变化的生物信息学/系统生物学分析表明，受影响的细胞途径/系统包括动脉粥样硬化、DM、纤维化、脂肪生成、细胞减少（细胞凋亡）和炎症。
