Apoh-KO Mouse

Apoh, also known as apolipoprotein H, is involved in lipid metabolism, regulating triglycerides, and is a component of HDL. It can bind free fatty acids, regulate the activity of many proteins involved in HDL metabolism, inhibit lipid transfer, and control the endogenous coagulation cascade. It also plays roles in complement and coagulation pathways [5,7].

In the context of antiphospholipid syndrome (APS), exosome-contained Apoh is associated with this disease. APS-exos, which contain Apoh, can cause APS-like birth outcomes, inhibit the migration and tube formation of human umbilical vein endothelial cells (HUVECs), and impair vascular development, leading to pregnancy complications. APOH-exos may play a role through the phospho-extracellular signal-regulated kinase pathway [1]. In addition, polymorphisms in the APOH gene are associated with susceptibility to recurrent pregnancy loss in women with APS [2].

In type 2 diabetic patients, Apoh plasma levels are significantly associated with triglycerides, components of triglyceride-rich lipoproteins, and RBP4 levels. Apoh is higher in type 2 diabetic patients with metabolic syndrome (MS) and with macrovascular disease, and the enhanced levels are due to increased liver synthesis [3]. In diabetic kidney disease (DKD) mice, the mRNA expression level of Apoh is declined [4]. Fructus arctii, a traditional medicinal plant, alleviates diabetic nephropathy progression by modulating cell proliferation and renal fibrosis via the Apoh/PPAR-γ pathway. Apoh overexpression suppresses high-glucose-induced cell proliferation and alleviates fibrosis in relevant cells [6].

In influenza-infected patients, low plasma levels of ApoH are associated with a worse prognosis, and adequate plasma levels of ApoH are protective against severe influenza and respiratory failure [7].

In summary, Apoh is crucial in lipid metabolism, HDL-related functions, and complement and coagulation pathways. Studies using models (such as mouse models in APS-related pregnancy complications, DKD, and diabetic nephropathy) have revealed its roles in various disease conditions, including APS, type 2 diabetes-related complications, DKD, and influenza-associated prognosis. These findings provide insights into the biological functions of Apoh and potential therapeutic targets for related diseases.

References:

1. Tan, Yuan, Bian, Yiding, Song, Yunfeng, Zhang, Qinhua, Wan, Xiaoping. 2021. Exosome-Contained APOH Associated With Antiphospholipid Syndrome. In Frontiers in immunology, 12, 604222. doi:10.3389/fimmu.2021.604222. https://pubmed.ncbi.nlm.nih.gov/34040601/

2. Deng, Xujing, Sang, Qing, Zhang, Ruixiu, Mu, Jian, Bao, Shihua. 2023. The association of APOH and NCF1 polymorphisms on susceptibility to recurrent pregnancy loss in women with antiphospholipid syndrome. In Journal of assisted reproduction and genetics, 40, 1703-1712. doi:10.1007/s10815-023-02829-5. https://pubmed.ncbi.nlm.nih.gov/37243946/

3. Castro, Antoni, Lázaro, Iolanda, Selva, David M, Simó, Rafael, Masana, Lluís. 2009. APOH is increased in the plasma and liver of type 2 diabetic patients with metabolic syndrome. In Atherosclerosis, 209, 201-5. doi:10.1016/j.atherosclerosis.2009.09.072. https://pubmed.ncbi.nlm.nih.gov/19878946/

4. Zhao, Jing, He, Kaiying, Du, Hongxuan, Zhou, Xiaochun, Wang, Jianqin. 2022. Bioinformatics prediction and experimental verification of key biomarkers for diabetic kidney disease based on transcriptome sequencing in mice. In PeerJ, 10, e13932. doi:10.7717/peerj.13932. https://pubmed.ncbi.nlm.nih.gov/36157062/

5. Deng, Siying, Xu, Yangkai, Zheng, Lemin. . HDL Structure. In Advances in experimental medicine and biology, 1377, 1-11. doi:10.1007/978-981-19-1592-5_1. https://pubmed.ncbi.nlm.nih.gov/35575917/

6. Zhang, Na, Chen, Anhui, Dong, Yuwei, Dou, Deqiang. 2025. Fructus arctii mitigates diabetic nephropathy via the Apoh/PPAR-γ pathway. In Molecular immunology, 181, 18-28. doi:10.1016/j.molimm.2025.02.017. https://pubmed.ncbi.nlm.nih.gov/40056629/

7. Garcinuño, Sara, Lalueza, Antonio, Gil-Etayo, Francisco Javier, Serrano, Antonio, Serrano, Manuel. 2024. Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis. In Frontiers in immunology, 15, 1443096. doi:10.3389/fimmu.2024.1443096. https://pubmed.ncbi.nlm.nih.gov/39176097/