Abstract 4363123: Spinal Cord Injury Alters the Abundance of Proteins Associated with High-Density Lipoprotein

Background: Individuals with spinal cord injury (SCI) have 3x the odds of heart disease and 4x the odds of stroke compared to age and sex-matched able-bodied people. This elevated CV risk is driven by a significant increase in atherosclerotic plaque formation, an effect maintained after accounting for traditional risk factors. While ASCVD after SCI presents a significant health risk, the mechanisms underlying this accelerated pathology have yet to be elucidated. Here, we utilized an exploratory approach to identify pathways related to ASCVD which are dysregulated after SCI. Methods: Mass spectrometry was performed on plasma from individuals with traumatic SCI (n=15; 8 males, 7 females; mean age 35.3 ± 14.5 years) and uninjured controls (n=15; 9 males, 6 females; mean age 36.5 ± 14.8 years). For SCI individuals, injuries were principally cervical (14 cervical, 1 thoracic) with ASIA impairment scores of A (n=10) or B (n=5); samples were collected 9.9 ± 3.8 weeks post-injury. Participants with a history of T2DM or CV events were excluded. Proteomic analysis used nano-liquid chromatography coupled to an Orbitrap Eclipse Tribrid. A data-dependent library was generated followed by sample analysis using data-independent acquisition. Data were processed in Spectronaut. Proteins with >20% missing values were excluded. Log-transformed intensities were compared by independent t-tests with false discovery rate correction. Gene Ontology (GO) enrichment was performed using ShinyGO. Results: Sixty-three differentially abundant proteins were identified. Notably, in the SCI group, Apolipoprotein A1 (ApoA1) was significantly downregulated (adj. p < 0.001; log2 fold change (SCI/Control) = –0.51), while Serum Amyloid A (SAA) was significantly upregulated (adj. p = 0.002; log2 fold change (SCI/Control) = 2.69). Other differentially abundant proteins included complement and coagulation factors. GO analysis revealed significant enrichment in molecular functions related to HDL particle receptor binding and cholesterol transfer activity. Conclusion: HDL is a key cardioprotective particle with a proteome known to be altered in inflammatory conditions, as evidenced by increased SAA and decreased ApoA1. This remodeling impairs HDL function, contributing to lipid accumulation in cells critical to plaque formation. Based on this data, we hypothesize that a driver of accelerated ASCVD after SCI is impaired HDL function. Future studies will evaluate HDL composition and function after SCI.