Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
NHC Key Laboratory of Viral Heart Diseases, Fudan University, Shanghai 200032, China.
Int J Mol Sci. 2021 Jul 9;22(14):7401. doi: 10.3390/ijms22147401.
Myocardial infarction (MI) is one of the most common cardiovascular diseases. Although previous studies have shown that histidine decarboxylase (HDC), a histamine-synthesizing enzyme, is involved in the stress response and heart remodeling after MI, the mechanism underlying it remains unclear. In this study, using -deficient mice ( mice), we established an acute myocardial infarction mouse model to explore the potential roles of /histamine in cardiac immune responses. Comprehensive analysis was performed on the transcriptomes of infarcted hearts. Differentially expressed gene (DEG) analysis identified 2126 DEGs in -deficient groups and 1013 in histamine-treated groups. Immune related pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we used the ssGSEA algorithm to evaluate 22 kinds of infiltrated immunocytes, which indicated that myeloid cells and T memory/follicular helper cells were tightly regulated by /histamine post MI. The relationships of lncRNAs and the Gene Ontology (GO) functions of protein-coding RNAs and immunocytes were dissected in networks to unveil immune-associated lncRNAs and their roles in immune modulation after MI. Finally, we screened out and verified four lncRNAs, which were closely implicated in tuning the immune responses after MI, including ENSMUST00000191157, ENSMUST00000180693 (PTPRE-AS1), and ENSMUST-00000182785. Our study highlighted the HDC-regulated myeloid cells as a driving force contributing to the government of transmission from innate immunocytes to adaptive immunocytes in the progression of the injury response after MI. We identified the potential role of the /histamine-lncRNAs network in regulating cardiac immune responses, which may provide novel promising therapeutic targets for further promoting the treatment of ischemic heart disease.
心肌梗死（MI）是最常见的心血管疾病之一。尽管先前的研究表明，组氨酸脱羧酶（HDC）作为一种组氨酸合成酶，参与 MI 后的应激反应和心脏重塑，但其中的机制尚不清楚。在本研究中，我们使用 HDC 缺陷型（Hdc-/-）小鼠建立了急性心肌梗死小鼠模型，以探讨 / 组胺在心脏免疫反应中的潜在作用。对梗死心脏的转录组进行了综合分析。差异表达基因（DEG）分析在 Hdc-/-组中鉴定出 2126 个 DEG，在组胺处理组中鉴定出 1013 个 DEG。京都基因与基因组百科全书（KEGG）分析富集了免疫相关途径。然后，我们使用 ssGSEA 算法评估 22 种浸润免疫细胞，结果表明髓样细胞和 T 记忆/滤泡辅助细胞在 MI 后受到 / 组胺的紧密调节。lncRNAs 与蛋白质编码 RNA 和免疫细胞的基因本体论（GO）功能之间的关系在网络中进行了剖析，以揭示免疫相关的 lncRNAs 及其在 MI 后免疫调节中的作用。最后，我们筛选并验证了四个与 MI 后免疫反应密切相关的 lncRNAs，包括 ENSMUST00000191157、ENSMUST00000180693（PTPRE-AS1）和 ENSMUST-00000182785。我们的研究强调了 HDC 调节的髓样细胞作为一种驱动力，有助于控制 MI 后损伤反应中固有免疫细胞向适应性免疫细胞的传递。我们确定了 / 组胺-lncRNAs 网络在调节心脏免疫反应中的潜在作用，这可能为进一步促进缺血性心脏病的治疗提供新的有前途的治疗靶点。
