Vcam1-KO Mouse

Vcam1, known as Vascular cell adhesion molecule 1, belongs to the immunoglobulin superfamily of cell adhesion molecules. It plays a crucial role in mediating the strong adherence of leukocytes to endothelial cells, regulating inflammation and leukocyte migration. It is involved in multiple biological processes such as lymphocyte recirculation and immune response, and is associated with numerous diseases including cancer, atherosclerosis, and asthma [3].

In gastric cancer, lactate in the tumor microenvironment promotes H3K18 lactylation, leading to transcriptional activation of Vcam1, which then activates AKT-mTOR signaling to enhance cell proliferation and migration. Also, Vcam1 upregulates CXCL1 expression via AKT-mTOR pathway, facilitating the recruitment of mesenchymal stem cells, immunesuppression, and cancer progression [1]. In ovarian cancer, the VLA4/VCAM1 pathway in macrophages and endothelial cells is involved in regulating vascular permeability and ascites development. Downregulating VLA4 or Vcam1 enhances cell adhesion and vascular integrity, abrogating ascites formation [2]. In sickle cell anemia, certain Vcam1 promoter haplotypes increase its expression, affecting systemic vasculopathy risk [4]. In liver fibrosis, Vcam1 expressed by liver sinusoidal endothelial cells promotes capillarization and fibrosis. Blocking Vcam1 can restore the phenotype of differentiated endothelial cells and reduce fibrosis-related markers in hepatic stellate cells [5]. In chronic cerebral hypoperfusion, increased Vcam1 expression on brain endothelial cells drives blood-brain-barrier impairment, and blocking Vcam1 activation alleviates this effect [6].

In conclusion, Vcam1 is essential for leukocyte adhesion, inflammation regulation, and immune response. Through gene-knockout or conditional-knockout mouse models and other functional studies, its role in various diseases has been revealed. These findings provide potential therapeutic targets for diseases such as cancer, ovarian cancer with ascites, sickle cell anemia, liver fibrosis, and chronic cerebral hypoperfusion-related neurodegenerative diseases.

References:

1. Zhao, Yupeng, Jiang, Jiang, Zhou, Peng, Li, Ranran, Xia, Jiazeng. 2024. H3K18 lactylation-mediated VCAM1 expression promotes gastric cancer progression and metastasis via AKT-mTOR-CXCL1 axis. In Biochemical pharmacology, 222, 116120. doi:10.1016/j.bcp.2024.116120. https://pubmed.ncbi.nlm.nih.gov/38461905/

2. Zhang, Shibo, Xie, Bingfan, Wang, Lijie, Liu, Changqing, He, Huanhuan. . Macrophage-mediated vascular permeability via VLA4/VCAM1 pathway dictates ascites development in ovarian cancer. In The Journal of clinical investigation, 131, . doi:10.1172/JCI140315. https://pubmed.ncbi.nlm.nih.gov/33295887/

3. Singh, Varinder, Kaur, Rupinder, Kumari, Pratima, Pasricha, Chirag, Singh, Ravinder. 2023. ICAM-1 and VCAM-1: Gatekeepers in various inflammatory and cardiovascular disorders. In Clinica chimica acta; international journal of clinical chemistry, 548, 117487. doi:10.1016/j.cca.2023.117487. https://pubmed.ncbi.nlm.nih.gov/37442359/

4. Silva, Marisa, Coelho, Andreia, Vargas, Sofia, Faustino, Paula. 2021. VCAM1, HMOX1 and NOS3 differential endothelial expression may impact sickle cell anemia vasculopathy. In Blood cells, molecules & diseases, 93, 102639. doi:10.1016/j.bcmd.2021.102639. https://pubmed.ncbi.nlm.nih.gov/34999313/

5. Guo, Qianqian, Furuta, Kunimaro, Islam, Shahidul, Hirsova, Petra, Ibrahim, Samar H. 2022. Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis. In Frontiers in immunology, 13, 983255. doi:10.3389/fimmu.2022.983255. https://pubmed.ncbi.nlm.nih.gov/36091042/

6. Zhang, Huiwen, Shang, Junkui, Li, Wei, Gao, Dandan, Zhang, Jiewen. 2024. Increased Expression of VCAM1 on Brain Endothelial Cells Drives Blood-Brain Barrier Impairment Following Chronic Cerebral Hypoperfusion. In ACS chemical neuroscience, 15, 2028-2041. doi:10.1021/acschemneuro.4c00039. https://pubmed.ncbi.nlm.nih.gov/38710594/