Single-Cell RNA-Seq Analysis Reveals Macrophage Involved in Pathogenesis of Human sporadic type A aortic dissection

Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in AD tissues by scRNA-seq. Ascending aortic wall tissue from 6 ATAAD patients and 3 heart transplant donors were assessed by scRNA-seq, then analyzed and validated by various bioinformatics algo-rithms and histopathology experiments. The results revealed the proportion of macrophages in AD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the 6 macro-phage subclusters, pro-inflammatory macrophages accounted for 14.96% in the AD group, and 0.18% in the normal group. Chemokine and inflammation related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in AD tissue than that in the normal tissues. Ad-ditionally, intercellular communication analysis and transcription factor analysis indicated activation of inflammation and degradation of the extracellular matrix in AD tissues. Finally, immunohisto-chemistry, immunofluorescence and western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in AD tissues. Collectively, our study provides a preliminary evaluation of the role of macrophages in AD and potentially aid in the development of therapeutic options in the future. We performed scRNA sequencing to understand macrophage function in in Pathogenesis of Human sporadic type A aortic dissection. We analyzed and validated by various bioinformatics algorithms and histopathology experiments.