Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, No.185, Juqian Street, Tianning District, Changzhou, 213003, Jiangsu Province, China.
J Cardiothorac Surg. 2024 May 7;19(1):280. doi: 10.1186/s13019-024-02760-5.
The long-term prognosis of patients with coronary artery disease (CAD) with diffuse long lesion underwent coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) remains worse. Here, we aimed to identify distinctive genes involved and offer novel insights into the pathogenesis of diffuse long lesion.
Whole exome sequencing was performed on peripheral blood samples from 20 CAD patients with diffuse long lesion (CAD-DLL) and from 10 controls with focal lesion (CAD-FL) through a uniform pipeline. Proteomics analysis was conducted on the serum samples from 10 CAD-DLL patients and from 10 controls with CAD-FL by mass spectrometry. Bioinformatics analysis was performed to elucidate the involved genes, including functional annotation and protein-protein interaction analysis.
A total of 742 shared variant genes were found in CAD-DLL patients but not in controls. Of these, 46 genes were identified as high-frequency variant genes (≥ 4/20) distinctive genes. According to the consensus variant site, 148 shared variant sites were found in the CAD-DLL group. The lysosome and cellular senescence-related pathway may be the most significant pathway in diffuse long lesion. Following the DNA-protein combined analysis, eight genes were screened whose expression levels were altered at both DNA and protein levels. Among these genes, the MAN2A2 gene, the only one that was highly expressed at the protein level, was associated with metabolic and immune-inflammatory dysregulation.
Compared to individuals with CAD-FL, patients with CAD-DLL show additional variants. These findings contribute to the understanding of the mechanism of CAD-DLL and provide potential targets for the diagnosis and treatment of CAD-DLL.
经冠状动脉旁路移植术（CABG）或经皮冠状动脉介入治疗（PCI）治疗的弥漫性长病变冠心病（CAD）患者的长期预后仍较差。在此，我们旨在确定涉及的独特基因，并为弥漫性长病变的发病机制提供新的见解。
通过统一的管道，对 20 例弥漫性长病变（CAD-DLL）CAD 患者和 10 例局灶性病变（CAD-FL）对照者的外周血样本进行全外显子测序。通过质谱法对 10 例 CAD-DLL 患者和 10 例 CAD-FL 对照者的血清样本进行蛋白质组学分析。进行生物信息学分析以阐明涉及的基因，包括功能注释和蛋白质-蛋白质相互作用分析。
在 CAD-DLL 患者中发现了 742 个共同的变异基因，但在对照组中没有发现。其中，有 46 个基因被确定为高频率变异基因（≥4/20）的独特基因。根据共识变异位点，在 CAD-DLL 组中发现了 148 个共同的变异位点。溶酶体和细胞衰老相关途径可能是弥漫性长病变中最重要的途径。在 DNA-蛋白联合分析后，筛选出 8 个在 DNA 和蛋白质水平上均发生改变的基因。在这些基因中，MAN2A2 基因是唯一在蛋白质水平上高表达的基因，与代谢和免疫炎症失调有关。
与 CAD-FL 个体相比，CAD-DLL 患者表现出更多的变异。这些发现有助于理解 CAD-DLL 的发病机制，并为 CAD-DLL 的诊断和治疗提供潜在的靶点。
