PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction.
PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction.
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DOI：
10.3389/fimmu.2022.878876
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
对于心力衰竭(HF)进展风险较高的急性心肌梗死(AMI)患者的早期诊断仍存在争议。本研究旨在识别新的预测急性心肌梗死后心衰的生物标志物，并揭示涉及这些标记基因的心衰的发病机制。应用加权基因共表达网络分析(WGCNA)分析了有心力衰竭进展(心梗后心力衰竭，n=16)和无心力衰竭进展(心梗后非心力衰竭，n=16)的急性心肌梗死患者的全血细胞转录数据集。结果表明，由720个HUB基因组成的一个模块与急性心肌梗死后心衰显著相关。HUB基因在另一个外周血单核细胞转录数据集(急性心肌梗死后心力衰竭，n=9；急性心肌梗死后非心力衰竭，n=8)中得到验证。PRKAR1A、SDCBP、SPRED2和VAMP3在两个数据集中上调。基于正常和梗死小鼠心脏组织中白细胞的单细胞RNA测序数据，进一步证实PRKAR1a在急性心肌梗死后第2天在单核/巨噬细胞中表达上调，而SDCBP在急性心肌梗死后第2天在中性粒细胞中高表达，在第3天在单核/巨噬细胞中高表达。细胞通讯分析表明，在配体-受体(L-R)对相互作用的基础上，MI急性期单核/巨噬细胞和中性粒细胞的自分泌/旁分泌串扰网络增加。对上述L受体基因与PRKAR1A和SDCBP的功能富集性分析表明，PRKAR1A和SDCBP主要参与炎症、细胞凋亡和血管生成。受试者工作特征(ROC)曲线分析表明，PRKAR1a和SDCBP及其组合在识别心力衰竭进展高危的急性心肌梗死患者中具有良好的预后价值。本研究证实了PRKAR1A和SDCBP可作为急性心肌梗死后心力衰竭早期诊断的新生物标志物，并揭示了它们在心力衰竭进展过程中的潜在调节机制。
Early diagnosis of patients with acute myocardial infarction (AMI) who are at a high risk of heart failure (HF) progression remains controversial. This study aimed at identifying new predictive biomarkers of post-AMI HF and at revealing the pathogenesis of HF involving these marker genes. A transcriptomic dataset of whole blood cells from AMI patients with HF progression (post-AMI HF, n = 16) and without progression (post-AMI non-HF, n = 16) was analyzed using the weighted gene co-expression network analysis (WGCNA). The results indicated that one module consisting of 720 hub genes was significantly correlated with post-AMI HF. The hub genes were validated in another transcriptomic dataset of peripheral blood mononuclear cells (post-AMI HF, n = 9; post-AMI non-HF, n = 8). PRKAR1A, SDCBP, SPRED2, and VAMP3 were upregulated in the two datasets. Based on a single-cell RNA sequencing dataset of leukocytes from heart tissues of normal and infarcted mice, PRKAR1A was further verified to be upregulated in monocytes/macrophages on day 2, while SDCBP was highly expressed in neutrophils on day 2 and in monocytes/macrophages on day 3 after AMI. Cell–cell communication analysis via the “CellChat” package showed that, based on the interaction of ligand–receptor (L–R) pairs, there were increased autocrine/paracrine cross-talk networks of monocytes/macrophages and neutrophils in the acute stage of MI. Functional enrichment analysis of the abovementioned L–R genes together with PRKAR1A and SDCBP performed through the Metascape platform suggested that PRKAR1A and SDCBP were mainly involved in inflammation, apoptosis, and angiogenesis. The receiver operating characteristic (ROC) curve analysis demonstrated that PRKAR1A and SDCBP, as well as their combination, had a promising prognostic value in the identification of AMI patients who were at a high risk of HF progression. This study identified that PRKAR1A and SDCBP may serve as novel biomarkers for the early diagnosis of post-AMI HF and also revealed their potentially regulatory mechanism during HF progression.
影响因子：
3.7
作者：
Azuaje F;Devaux Y;Wagner DR
通讯作者：
Wagner DR