Proteomic analysis of carotid artery plaques with and without vulnerable features on magnetic resonance angiography with vessel wall imaging: a pilot study

Objective: Extracranial carotid artery pathology accounts for 15% to 20% of ischemic strokes. Advancements in magnetic resonance angiography (MRA) with vessel wall imaging (VWI) have enabled the identification of vulnerable plaques, aiding in risk stratification for neurovascular events. This pilot study aimed to identify proteins in plaques with and without vulnerable features on MRA with VWI. Methods: Consecutive patients undergoing carotid endarterectomy were included in the study cohort with preoperative MRA with VWI. A retrospective chart review was conducted to extract pertinent clinical data including cardiovascular risk factors and medications. Proteomic analysis involved Tandem Mass Tag (TMTpro) labeling of peptides, basic pH high-performance liquid chromatography fractionation, and NanoLC-tandem mass spectrometry. Results: Proteomic analysis revealed 23 proteins significantly elevated in vulnerable plaques, including Proteinase 3 (PRTN3), Phospholipid Transfer Protein (PLTP), and S100 Calcium-Binding Protein A12 (S100A12), with increased abundance exceeding two-fold changes or above (P < .001). Conversely, three proteins exhibited reduced abundance in vulnerable plaques including Dynamin-3 (DNM3), Transmembrane Protein 181 (TMEM181), and Adducin-3 (ADD3) (P < .05). Conclusions: This study contributes to the understanding of protein biomarkers associated with carotid plaque vulnerability, offering insights into disease progression and stroke prevention. Proteins secreted by vulnerable plaques may offer not only the potential for early disease recognition; but can also become a target for future pharmacologic therapy prior to a devastating neurologic event. Further validation studies and multi-center trials will be needed to confirm the value of these potential biomarkers.