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解析乳酸相关基因在心肌梗死中的作用。

Unraveling the role of lactate-related genes in myocardial infarction.

作者信息

Xu Rui, Li YanYan, Xu Hong, Lai HongMei

机构信息

Gerontology Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, China.

Department of Cardiac Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, China.

出版信息

Heliyon. 2024 Sep 19;10(18):e38152. doi: 10.1016/j.heliyon.2024.e38152. eCollection 2024 Sep 30.

DOI:10.1016/j.heliyon.2024.e38152
PMID:39347425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11437837/
Abstract

BACKGROUND

Lactate is a crucial intermediary, facilitating communication between myocardial energy metabolism and microenvironmental regulation. The present study aimed to investigate the relationship between lactate-related genes (LRGs) and myocardial infarction (MI).

METHODS

A total of 23 LRGs exhibited differential expression between individuals with MI and healthy controls. Lasso regression analysis and validation with the GSE61144 dataset identified three hub genes: COX20, AGK, and PDHX. Single-gene GSEA of these genes revealed strong enrichment in pathways related to amino acid metabolism, cell cycle, and immune functions. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was utilized to validate the expression levels of the hub genes.

RESULTS

Immune infiltration analysis revealed differences in CD4 T and CD8 T cells between the MI and control groups. Additionally, 67 candidate drugs targeting the three hub LRGs were identified, and a ceRNA network was constructed to explore the intricate interactions among these genes.

CONCLUSIONS

These findings enhance the understanding of MI and have potential therapeutic implications.

摘要

背景

乳酸是一种关键的中间产物，有助于心肌能量代谢与微环境调节之间的沟通。本研究旨在探讨乳酸相关基因（LRGs）与心肌梗死（MI）之间的关系。

方法

共有23个LRGs在MI患者和健康对照者之间表现出差异表达。通过套索回归分析并使用GSE61144数据集进行验证，确定了三个核心基因：COX20、AGK和PDHX。对这些基因进行单基因基因集富集分析（GSEA）发现，它们在与氨基酸代谢、细胞周期和免疫功能相关的通路中高度富集。采用定量逆转录聚合酶链反应（qRT-PCR）验证核心基因的表达水平。

结果

免疫浸润分析显示MI组和对照组之间CD4 T细胞和CD8 T细胞存在差异。此外，鉴定出67种靶向三个核心LRGs的候选药物，并构建了一个竞争性内源性RNA（ceRNA）网络以探索这些基因之间的复杂相互作用。

结论

这些发现加深了对MI的理解，并具有潜在的治疗意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/f5d0a7cda8fa/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/29da2f52b812/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/a73fdb099336/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/6b079418c2a1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/a79d52195ec5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/6dddfab8aa79/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/9204d10d4d5c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/4533f4f5fe83/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/f5d0a7cda8fa/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/29da2f52b812/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/a73fdb099336/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/6b079418c2a1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/a79d52195ec5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/6dddfab8aa79/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/9204d10d4d5c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/4533f4f5fe83/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5d/11437837/f5d0a7cda8fa/gr8.jpg

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本文引用的文献

1
Lactate and lactylation: Behind the development of tumors.乳酸和乳酸化：肿瘤发展的背后。
Cancer Lett. 2024 Jun 1;591:216896. doi: 10.1016/j.canlet.2024.216896. Epub 2024 Apr 17.
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Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway.辅酶 Q10 通过 NLRP3/IL1β 途径减轻心肌梗死后巨噬细胞介导的心肌炎症。
BMC Cardiovasc Disord. 2024 Jan 28;24(1):76. doi: 10.1186/s12872-024-03729-x.
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Association between normalized lactate load and in-hospital mortality in patients with acute myocardial infarction.
急性心肌梗死患者中标准化乳酸负荷与院内死亡率之间的关联。
Int J Cardiol. 2024 Mar 15;399:131658. doi: 10.1016/j.ijcard.2023.131658. Epub 2023 Dec 23.
4
High serum lactate dehydrogenase as a predictor of cardiac insufficiency at follow-up in elderly patients with acute myocardial infarction.血清乳酸脱氢酶水平升高可预测老年急性心肌梗死患者随访中心力衰竭的发生。
Arch Gerontol Geriatr. 2024 Feb;117:105253. doi: 10.1016/j.archger.2023.105253. Epub 2023 Oct 29.
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The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.糖酵解代谢途径在心血管疾病中的作用及潜在治疗方法。
Basic Res Cardiol. 2023 Nov 8;118(1):48. doi: 10.1007/s00395-023-01018-w.
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Association between lactate/albumin ratio and prognosis in patients with acute myocardial infarction.急性心肌梗死患者乳酸/白蛋白比值与预后的关系
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Oncogene-mediated nuclear accumulation of lactate promotes epigenetic alterations to induce cancer cell proliferation.癌基因介导的乳酸在核内的积累促进了表观遗传改变，从而诱导癌细胞增殖。
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