Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics
Abstract This study investigated Hippo signaling pathway-related biomarkers in acute myocardial infarction (AMI). First, differentially expressed genes (DEGs) between AMI patients and controls were identified. Consensus clustering then classified AMI subtypes, followed by subtype-specific DEG screen...
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-94820-6 |
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| author | Xingda Li Xueqi He Yu Zhang Xinyuan Hao Anqi Xiong Jiayu Huang Biying Jiang Zaiyu Tong Haiyan Huang Lian Yi Wenjia Chen |
| author_facet | Xingda Li Xueqi He Yu Zhang Xinyuan Hao Anqi Xiong Jiayu Huang Biying Jiang Zaiyu Tong Haiyan Huang Lian Yi Wenjia Chen |
| author_sort | Xingda Li |
| collection | DOAJ |
| description | Abstract This study investigated Hippo signaling pathway-related biomarkers in acute myocardial infarction (AMI). First, differentially expressed genes (DEGs) between AMI patients and controls were identified. Consensus clustering then classified AMI subtypes, followed by subtype-specific DEG screening. Candidate genes were derived from intersecting initial DEGs with subtype-associated DEGs. Three machine-learning algorithms prioritized five biomarkers (NAMPT, CXCL1, CREM, GIMAP6, and GIMAP7), validated through multi-dataset analyses and cellular expression profiling. qRT-PCR and Western blot confirmed differential expression patterns between AMI and controls across experimental models. Notably, NAMPT, CXCL1, and GIMAP6 exhibited cell-type-specific expression in endothelial cells and macrophages. We further predicted 179 potential therapeutic agents targeting these biomarkers. Niclosamide and eugenol were observed to mitigate hypoxia-induced injury in neonatal mouse ventricular cardiomyocytes. In vivo experiments demonstrated upregulated NAMPT/CXCL1 and downregulated GIMAP6/GIMAP7 in AMI myocardial tissues, with significant NAMPT protein elevation. These biomarkers show clinical diagnostic potential and provide mechanistic insights into AMI pathogenesis. |
| format | Article |
| id | doaj-art-eaab6ff74a1141f285e5fd79ffe8fead |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-eaab6ff74a1141f285e5fd79ffe8fead2025-08-20T02:10:16ZengNature PortfolioScientific Reports2045-23222025-03-0115112010.1038/s41598-025-94820-6Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomicsXingda Li0Xueqi He1Yu Zhang2Xinyuan Hao3Anqi Xiong4Jiayu Huang5Biying Jiang6Zaiyu Tong7Haiyan Huang8Lian Yi9Wenjia Chen10National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education; International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy, Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital, and Department of Pharmacology at College of Pharmacy (The Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital, and Department of Pharmacology at College of Pharmacy (The Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital, and Department of Pharmacology at College of Pharmacy (The Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Cardiology, First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, First Affiliated Hospital of Harbin Medical UniversityDepartment of Neurology, First Affiliated Hospital of Harbin Medical UniversityDepartment of Neurology, First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, First Affiliated Hospital of Harbin Medical UniversityAbstract This study investigated Hippo signaling pathway-related biomarkers in acute myocardial infarction (AMI). First, differentially expressed genes (DEGs) between AMI patients and controls were identified. Consensus clustering then classified AMI subtypes, followed by subtype-specific DEG screening. Candidate genes were derived from intersecting initial DEGs with subtype-associated DEGs. Three machine-learning algorithms prioritized five biomarkers (NAMPT, CXCL1, CREM, GIMAP6, and GIMAP7), validated through multi-dataset analyses and cellular expression profiling. qRT-PCR and Western blot confirmed differential expression patterns between AMI and controls across experimental models. Notably, NAMPT, CXCL1, and GIMAP6 exhibited cell-type-specific expression in endothelial cells and macrophages. We further predicted 179 potential therapeutic agents targeting these biomarkers. Niclosamide and eugenol were observed to mitigate hypoxia-induced injury in neonatal mouse ventricular cardiomyocytes. In vivo experiments demonstrated upregulated NAMPT/CXCL1 and downregulated GIMAP6/GIMAP7 in AMI myocardial tissues, with significant NAMPT protein elevation. These biomarkers show clinical diagnostic potential and provide mechanistic insights into AMI pathogenesis.https://doi.org/10.1038/s41598-025-94820-6Acute myocardial infarctionHippo signaling pathwayBiomarkersImmune infiltrationEndothelial cellMacrophage |
| spellingShingle | Xingda Li Xueqi He Yu Zhang Xinyuan Hao Anqi Xiong Jiayu Huang Biying Jiang Zaiyu Tong Haiyan Huang Lian Yi Wenjia Chen Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics Scientific Reports Acute myocardial infarction Hippo signaling pathway Biomarkers Immune infiltration Endothelial cell Macrophage |
| title | Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics |
| title_full | Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics |
| title_fullStr | Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics |
| title_full_unstemmed | Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics |
| title_short | Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics |
| title_sort | uncovering hippo pathway related biomarkers in acute myocardial infarction via scrna seq binding transcriptomics |
| topic | Acute myocardial infarction Hippo signaling pathway Biomarkers Immune infiltration Endothelial cell Macrophage |
| url | https://doi.org/10.1038/s41598-025-94820-6 |
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