INCLIVA health Research Institute, 46010 Valencia, Spain.
Centro de Biomateriales e Ingeniería Tisular, Universidad Politécnica de Valencia, 46022 Valencia, Spain.
Int J Mol Sci. 2022 Dec 9;23(24):15615. doi: 10.3390/ijms232415615.
Extracellular matrix (ECM) changes after myocardial infarction (MI) need precise regulation, and next-generation sequencing technologies provide omics data that can be used in this context. We performed a meta-analysis using RNA-sequencing transcriptomic datasets to identify genes involved in post-MI ECM turnover. Eight studies available in Gene Expression Omnibus were selected following the inclusion criteria. We compare RNA-sequencing data from 92 mice submitted to permanent coronary ligation or sham, identifying differentially expressed genes (p-value < 0.05 and Log2FoldChange ≥ 2). Functional enrichment analysis was performed based on Gene Ontology biological processes (BPs). BPs implicated in response to extracellular stimulus, regulation of ECM organization, and ECM disassembly were detected soon after ischemia onset. ECM disassembly occurred between days one to seven post-MI, compared with ECM assembly from day seven onwards. We identified altered mRNA expression of 19 matrix metalloproteinases and four tissue inhibitors of metalloproteinases at post-infarcted ECM remodeling and altered transcriptomic expression of 42 genes encoding 26 collagen subunits at the fibrotic stage. To our knowledge, this is the first meta-analysis using RNA-sequencing datasets to evaluate post-infarcted cardiac interstitium healing, revealing previously unknown mechanisms and molecules actively implicated in ECM remodeling post-MI, which warrant further validation.
细胞外基质（ECM）在心肌梗死后需要精确调节，下一代测序技术提供了可以在此背景下使用的组学数据。我们使用 RNA 测序转录组数据集进行了荟萃分析，以鉴定与梗死后 ECM 周转相关的基因。根据纳入标准，从 Gene Expression Omnibus 中选择了 8 项研究。我们比较了 92 只接受永久性冠状动脉结扎或假手术的小鼠的 RNA 测序数据，鉴定出差异表达的基因（p 值<0.05，Log2FoldChange≥2）。基于基因本体论（GO）生物过程（BP）进行功能富集分析。在缺血发作后不久，检测到与细胞外刺激反应、ECM 组织调节和 ECM 解体相关的 BP。与梗死后第 7 天开始的 ECM 组装相比，ECM 解体发生在第 1 天至第 7 天之间。我们在梗死后 ECM 重塑时发现 19 种基质金属蛋白酶和 4 种金属蛋白酶组织抑制剂的 mRNA 表达发生改变，在纤维化阶段发现 42 个编码 26 种胶原亚基的基因的转录组表达发生改变。据我们所知，这是首次使用 RNA 测序数据集评估梗死后心脏间质愈合的荟萃分析，揭示了先前未知的机制和分子，它们积极参与梗死后的 ECM 重塑，值得进一步验证。
