2. Academic Validation
  3. Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics

Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics

  • Sci Rep. 2025 Mar 26;15(1):10368. doi: 10.1038/s41598-025-94820-6.
Xingda Li # 1 2,  Xueqi He # 2,  Yu Zhang 2,  Xinyuan Hao 2,  Anqi Xiong 3,  Jiayu Huang 3,  Biying Jiang 3,  Zaiyu Tong 3,  Haiyan Huang 4,  Lian Yi 5,  Wenjia Chen 6
Affiliations

Affiliations

  • 1 National 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 University, Harbin, 150086, Heilongjiang, People's Republic of China.
  • 2 Department 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 University, Harbin, 150086, People's Republic of China.
  • 3 Department of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang Province, People's Republic of China.
  • 4 Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
  • 5 Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China. yilian@hrbmu.edu.cn.
  • 6 Department of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, 150001, Heilongjiang Province, People's Republic of China. chenwenjia0725@163.com.
  • # Contributed equally.
PMID: 40133574 DOI: 10.1038/s41598-025-94820-6
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.

Keywords

Acute myocardial infarction; Biomarkers; Endothelial cell; Hippo signaling pathway; Immune infiltration; Macrophage.

Figures
Products