Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes.

Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell–cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery.

Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.

背景：尽管许多病理变化与缺血性心脏病（IHD）相关，但缺血性心肌特有的分子水平变化及其反映疾病严重程度或治疗结果的潜力仍不清楚。目前，诊断相对较晚，并且评估疾病严重程度主要基于临床症状、各种成像方式或危险因素的确定。本研究旨在从心房心肌中鉴定与 IHD 相关的特征 RNA，并评估它们反映疾病严重程度或心脏手术结果的能力。

方法和结果：我们收集了 40 名接受冠状动脉搭桥手术的侵入性冠状动脉造影 (ICA) 阳性 IHD 患者和 8 名接受瓣膜手术的 ICA 阴性 IHD（非 IHD）患者的右心耳 (RAA) 活检。RNA 测序后，针对 GTEx 项目中 429 名没有心脏病的捐赠者进行了 RAA 转录组分析。IHD 转录组的特点是细胞间接触和线粒体功能障碍途径中的 RNA 表达受到抑制。增加了表达量CSRNP3、FUT10、SHD、NAV2-AS4，和 hsa-mir-181 基因与冠状动脉阻塞的复杂性具有显着性，或与搭桥手术的功能性心脏益处相关。

结论：我们的结果提供了对 IHD 特征 RNA 的以心房心肌为中心的见解。这里描述的特定基因表达变化为未来基于疾病机制的生物标志物鉴定铺平了道路，以用于 IHD 的早期检测和治疗。