Extracellular vesicles loaded with ApoB-100 protein affect the occurrence of coronary heart disease in patients after injury of spinal cord

• Published in: International journal of biological macromolecules 2024-10, Vol.277 (Pt 4), p.134330, Article 134330
• Main Authors: Wu, Chunshuai, Chen, Jiajia, Zhang, Jinlong, Hong, Hongxiang, Jiang, Jiawei, Ji, Chunyan, Li, Chaochen, Xia, Mingjie, Xu, Guanhua, Cui, Zhiming
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Vesicular Transport - genetics; Adaptor Proteins, Vesicular Transport - metabolism; Animals; APOB-100; Apolipoprotein B-100 - metabolism; Apoptosis; Coronary Disease - metabolism; Coronary Disease - pathology; Coronary heart disease; Disease Models, Animal; Extracellular vesicles; Extracellular Vesicles - metabolism; Female; Humans; Injury of spinal cord; Macrophages - metabolism; Male; Middle Aged; Neurons - metabolism; Rats; Rats, Sprague-Dawley; Sortilin; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.134330

Spinal cord injury (SCI) patients have an increased susceptibility to coronary heart disease (CHD) due to dysregulated lipid deposition. We conducted a comprehensive investigation to gain insights into the specific roles of Apolipoprotein B-100 (APOB-100) in the development of CHD in patients suffering from SCI. First, we established an SCI rat model through semitransection. APOB-100 expression in plasma exosomes obtained from patients were determined. Subsequently, we found APOB-100 affected macrophage polarization when treating co-cultured neurons/macrophages lacking Sortilin with extracellular vesicles derived from SCI rats, where APOB-100 co-immunoprecipitated with Sortilin. Moreover, APOB-100 upregulation reduced neuronal cell viability and triggered apoptosis by upregulating Sortilin, leading to a decline in the Basso, Beattie, and Bresnahan (BBB) scale, exacerbation of neuron injury, increased macrophage infiltration, and elevated blood lipid-related indicators in SCI rats, which could be reversed by silencing Sortilin. In conclusion, APOB-100 from post-SCI patients' extracellular vesicles upregulates Sortilin, thereby endangering those patients to CHD.