Misfolded plasma protein signature in carotid artery dissection

Background and objectives Carotid artery dissection (CaAD) is a significant cause of ischaemic stroke in young adults, accounting for up to 5% of cases in individuals under 45 years of age. Despite its clinical relevance, the molecular mechanisms underlying CaAD remain poorly understood. Structural weakening of the arterial wall, possibly resulting from disrupted cellular protein homeostasis and the accumulation of misfolded proteins, is considered a key factor. However, the presence and potential role of misfolded or damaged proteins released into circulation remain largely unexplored. This study aimed to detect, identify, and quantify misfolded proteins in the plasma of patients with CaAD. Methods Plasma samples from 21 patients with CaAD and 21 healthy controls were collected at the Military University Hospital Prague between 2021 and 2024. Misfolded proteins were isolated using a surface plasmon resonance biosensor combined with the Heat-shock protein 70 Trap assay and analysed by liquid chromatography with tandem mass spectrometry. Proteomic data were statistically evaluated to identify significant differences in protein levels between groups. Results A total of 38 proteins showed significant quantitative differences between patients and controls. These proteins were primarily involved in cell adhesion (Desmoplakin, Plakophilin-1, Plakoglobin), inflammation (Platelet Basic Protein), coagulation (Kininogen-1, Vitamin K-dependent Protein S), and lipid metabolism (Apolipoproteins C-I, C-II, C-III, and E). These alterations may contribute to endothelial dysfunction and the loss of vascular wall stability. Based on these findings, a five-protein biomarker panel was constructed. This panel distinguished CaAD patients from healthy controls with high accuracy (AUC = 0.984), achieving 93.3% sensitivity and 100% specificity. Discussion This study identified a distinct proteomic signature in the plasma of patients with CaAD, providing evidence for early disturbances in immunoregulation, coagulation, and lipid metabolism in CaAD pathogenesis. The results support the hypothesis that impaired proteostasis contributes to vascular dysfunction and may underlie the molecular mechanisms of CaAD. The identified proteins represent promising biomarker candidates for detecting individuals at increased risk of CaAD. Further large-scale studies are warranted to validate these findings and explore their potential clinical utility in early diagnosis and risk stratification.