Molecular landscape of atherosclerotic plaque progression: insights from proteomics, single-cell transcriptomics and genomics

作者：Chaonan Wang, Yuyao Feng, Xiaoyan Liu, Haidan Sun, Zhengguang Guo, Jiang Shao, Kang Li, Junye Chen, Keqiang Shu, Deqiang Kong, Jiaxian Wang, Yiran Li, Xiangling Lei, Chen Li, Bao Liu, Wei Sun, Zhichao Lai · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-04058-2 · 被引用次数：7 · 研究领域：Single-cell and spatial transcriptomics、Atherosclerosis and Cardiovascular Diseases、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUNDS: Atherosclerosis is a major contributor to cardiovascular diseases worldwide. Despite advancements in understanding its pathology, significant gaps remain in the molecular characterization of atherosclerotic plaques. This study addresses this gap by extensively profiling the proteomic landscape of carotid atherosclerotic plaques, classified under the American Heart Association (AHA) types IV to VI, to identify potential biomarkers and therapeutic targets. METHODS: The study employed an integrated approach using data-independent acquisition (DIA) proteomics, single-cell RNA sequencing, and Mendelian randomization (MR). A total of 87 human carotid plaques were analyzed to identify and quantify protein expression. These proteins were then mapped to specific regions within the plaques, such as the fibrous cap and lipid core, and further validated in independent samples and single-cell datasets. Furthermore, Mendelian randomization techniques were employed to assess causal relationships between identified proteins levels and ischemic stroke. RESULTS: The proteomic analysis of the 87 carotid plaques revealed 6143 proteins, highlighting diverse expression profiles across different plaque stages. Notably, proteins like CD44 and GAL-1 were predominantly expressed in the fibrous cap, suggesting a role in plaque stability, while TREM2, SMAD3, and IL-6R showed higher expression in the lipid core, indicating involvement in inflammatory processes. These findings were further co...