Spatial Proteomics Profiling of Vascular Smooth Muscle Cells and Atherosclerotic Plaques in a Diabetic Atherosclerosis Mouse Model
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ABSTRACT: This project presents a spatial proteomic investigation of vascular smooth muscle cells (VSMCs) and atherosclerotic plaque regions in a diabetic mouse model of atherosclerosis (DMAS). Using ApoE-/- mice fed with a high-fat diet and treated with low-dose streptozotocin (STZ) to induce a diabetic phenotype, we performed laser capture microdissection (LCM) to separately isolate plaque regions and adjacent VSMC-rich areas of the aortic arch. Subsequently, spatially resolved proteomic profiling was carried out using LC-MS/MS, followed by quantitative analysis based on iBAQ values. Differentially expressed proteins between plaque and VSMC regions were identified and enriched pathway analysis revealed significant alterations in oxidative stress response, insulin signaling, mitochondrial function, RNA transport, and extracellular matrix remodeling under diabetic conditions. Of particular interest, the spatial proteomics data highlighted a marked downregulation of the nuclear pore complex protein Nup93 in VSMCs from diabetic mice, implicating impaired nuclear transport and dysregulation of RNA alternative splicing. This finding was supported by transcriptomic integration and functional analyses that revealed aberrant splicing of SerpinE2, a gene associated with cell proliferation and ECM accumulation. This dataset provides region-specific, high-resolution proteomic profiles of vascular tissues in a diabetic atherosclerosis model. It serves as a valuable resource for investigating the spatial heterogeneity of vascular pathology and the molecular mechanisms underlying diabetes-accelerated atherosclerosis. The raw and processed data can be used to explore protein expression dynamics, identify spatiotemporal biomarkers, and validate candidate targets such as Nup93 and SerpinE2 involved in VSMC phenotypic switching.
INSTRUMENT(S):
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Aortic Arch
SUBMITTER:
Yuan Xiaojing
LAB HEAD: Xiaojing Yuan
PROVIDER: PXD063231 | Pride | 2025-09-29
REPOSITORIES: Pride
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