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The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages 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 ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.<\/jats:p>","DOI":"10.3390\/biom13020399","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T02:07:44Z","timestamp":1676945264000},"page":"399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Single-Cell RNA-Seq Analysis Reveals Macrophages Are Involved in the Pathogenesis of Human Sporadic Acute Type A Aortic Dissection"],"prefix":"10.3390","volume":"13","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Cong","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Qi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jia","family":"Qiang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 528406, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Yang","sequence":"additional","affiliation":[{"name":"Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Ping","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510920, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"},{"name":"Department of Cardiothoracic Surgery, University Hospital, University Link\u00f6ping, 58183 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1001\/jamacardio.2022.2718","article-title":"Early Mortality in Type A Acute Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection","volume":"7","author":"Harris","year":"2022","journal-title":"JAMA Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/S0140-6736(14)61005-9","article-title":"Management of acute aortic dissection","volume":"385","author":"Nienaber","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/j.jacc.2020.07.061","article-title":"Type A Aortic Dissection-Experience Over 5 Decades: JACC Historical Breakthroughs in Perspective","volume":"76","author":"Zhu","year":"2020","journal-title":"J. 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