Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.
Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.
复制标题
DOI：
10.1038/s44161-022-00171-0
复制
发表时间：
2022-12
期刊：
影响因子：
--
通讯作者：
M. Mokry;A. Boltjes;L. Slenders;Gemma Bel-Bordes;Kai Cui;E. Brouwer;J. Mekke;M. Depuydt;N. Timmerman;F. Waissi;M. Verwer;A. Turner;Mohammad Daud Khan;C. Hodonsky;E. Diez Benavente;R. Hartman;N. V. D. van den Dungen;N. Lansu;Emilia Nagyova;K. Prange;J. Kovacic;J. Björkegren;Eleftherios Pavlos;E. Andreakos;H. Schunkert;G. Owens;C. Monaco;A. Finn;R. Virmani;N. Leeper;M. D. de Winther;J. Kuiper;G. D. de Borst;E. Stroes;M. Civelek;D. D. de Kleijn-D.;H. D. den Ruijter;F. Asselbergs;S. W. van der Laan;Clint L. Miller;G. Pasterkamp
中科院分区：
文献类型：
--
作者：
M. Mokry;A. Boltjes;L. Slenders;Gemma Bel-Bordes;Kai Cui;E. Brouwer;J. Mekke;M. Depuydt;N. Timmerman;F. Waissi;M. Verwer;A. Turner;Mohammad Daud Khan;C. Hodonsky;E. Diez Benavente;R. Hartman;N. V. D. van den Dungen;N. Lansu;Emilia Nagyova;K. Prange;J. Kovacic;J. Björkegren;Eleftherios Pavlos;E. Andreakos;H. Schunkert;G. Owens;C. Monaco;A. Finn;R. Virmani;N. Leeper;M. D. de Winther;J. Kuiper;G. D. de Borst;E. Stroes;M. Civelek;D. D. de Kleijn-D.;H. D. den Ruijter;F. Asselbergs;S. W. van der Laan;Clint L. Miller;G. Pasterkamp
组织学研究揭示了动脉粥样硬化斑块血栓形成的关键过程。然而，病变类型的多样性和复杂性突出了改善亚表型的需要。在这里，我们分析了654个先进的人类颈动脉斑块的基因表达谱。无监督的转录组驱动的聚类揭示了五种主要的斑块类型。这些斑块表型与临床表现相关，并显示细胞组成的差异。冠状动脉段的验证表明，这些斑块的分子特征与冠状动脉缺血有关。具有最严重临床症状的斑块类型之一指向炎症和纤维化细胞谱系。此外，我们对标记不同斑块表型的潜在循环生物标志物进行了初步分析。总之，血栓事件风险斑块的定义可以通过深入的基于转录组学的表型进行微调。这些不同的斑块表型证明与颈动脉和冠状动脉斑块临床相关，并指出不同的潜在生物学的症状性病变。
Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved subphenotyping. Here, we analyzed the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Furthermore, we did a preliminary analysis of potential circulating biomarkers that mark the different plaque phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.