Plasma proteins misfolded in carotid artery dissection patients

Carotid artery dissection, a tear in the wall of one of the arteries supplying the brain, is a leading cause of ischaemic stroke in young and middle-aged adults, accounting for up to 5% of strokes in people under 45. Yet the molecular events that weaken the arterial wall in the first place have remained poorly understood. A new study now reports that the blood plasma of patients with carotid artery dissection carries a measurable signature of misfolded and altered proteins, pointing to disturbances in protein homeostasis, inflammation, coagulation and lipid metabolism that may accompany the disease.

Researchers at the Military University Hospital Prague collected plasma samples from 21 patients with carotid artery dissection and 21 healthy controls between 2021 and 2024. Rather than measuring total protein abundance in the usual way, the team set out to detect proteins in an altered, misfolded state circulating in the bloodstream, a possibility that had remained largely unexplored in this condition.

To isolate these aberrant proteins, the investigators used a surface plasmon resonance biosensor combined with a Heat-shock protein 70 Trap assay. Heat-shock protein 70 acts as a molecular chaperone that preferentially binds proteins with damaged or non-native conformations, so trapping complexes containing it provides a way to enrich for misfolded species from plasma. The captured proteins were then identified and quantified by liquid chromatography with tandem mass spectrometry, and the resulting proteomic data were statistically evaluated to find proteins whose levels differed significantly between patients and controls.

The analysis revealed 38 proteins with significant quantitative differences between the two groups. Many of them cluster into functional categories that make biological sense for a disease of the arterial wall. Among the proteins elevated or altered in patients were Desmoplakin, Plakophilin-1 and Plakoglobin, which are involved in cell adhesion, as well as Platelet Basic Protein, linked to inflammation, Kininogen-1 and Vitamin K-dependent Protein S, both tied to coagulation, and the apolipoproteins C-I, C-II, C-III and E, central players in lipid metabolism.

The study’s authors suggest that these alterations may contribute to endothelial dysfunction and to the loss of vascular wall stability, processes that could plausibly underlie the structural weakening of the artery that precedes dissection. The findings are consistent with the hypothesis that impaired proteostasis, the cellular system that keeps proteins correctly folded and functional, contributes to vascular dysfunction in this disease and may be part of its molecular mechanism.

Beyond the biological insight, the work yielded a potential clinical tool. From the 38 differentially abundant proteins, the researchers constructed a five-protein biomarker panel. In their dataset, this panel distinguished carotid artery dissection patients from healthy controls with an area under the curve of 0.984, corresponding to 93.3% sensitivity and 100% specificity. An area under the curve of this magnitude indicates near-perfect separation between the two groups in this sample.

Such performance figures, however, come from a small, single-centre study with only 21 patients and 21 controls, and they reflect how well the panel separates known cases from known controls rather than how it would perform as a screening test in the general population. The authors themselves emphasise that further large-scale studies are needed to validate the findings and to explore whether the protein signature could be useful for early diagnosis or risk stratification in clinical practice.

Even with those caveats, the study adds a new dimension to research on carotid artery dissection, which has traditionally focused on structural and genetic factors affecting the arterial wall. The identification of a distinct plasma proteomic signature provides evidence for early disturbances in immunoregulation, coagulation and lipid metabolism in the disease’s pathogenesis, and it suggests that damaged or misfolded proteins released into the circulation could serve as both mechanistic clues and biomarker candidates for identifying individuals at increased risk.

The research, published as an open-access article in the journal Clinical Proteomics, was led by Petr Malý and Jan M. Horáček along with colleagues including Leona Chrastinová and Martin Malý. If the five-protein panel holds up in larger and more diverse cohorts, it could eventually help clinicians recognise people at heightened risk of carotid artery dissection before the vessel fails, though that prospect remains a goal for future validation studies rather than a current clinical reality.

Subject of Research: Misfolded plasma protein signatures in carotid artery dissection

Article Title: Misfolded plasma protein signature in carotid artery dissection

Article References: Malý, P., Chrastinová, L., Malý, M., & Horáček, J. M. (2026). Misfolded plasma protein signature in carotid artery dissection. Clinical Proteomics. https://doi.org/10.1186/s12014-026-09647-8

Image Credits: AI Generated

DOI: 10.1186/s12014-026-09647-8

Keywords: carotid artery dissection, misfolded proteins, proteomics, biomarker panel, ischaemic stroke, protein homeostasis, mass spectrometry, lipid metabolism, coagulation, inflammation, vascular biology, Misfolded