An intersegmental single-cell profile reveals aortic heterogeneity and identifies a novel Malat1(+) vascular smooth muscle subtype involved in abdominal aortic aneurysm formation.
An intersegmental single-cell profile reveals aortic heterogeneity and identifies a novel Malat1(+) vascular smooth muscle subtype involved in abdominal aortic aneurysm formation.
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DOI：
10.1038/s41392-022-00943-x
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发表时间：
2022-04-27
影响因子：
39.3
通讯作者：
Zhang, Cheng
中科院分区：
文献类型：
--
作者：
Yu, Liwen;Zhang, Jie;Gao, Amy;Zhang, Meng;Wang, Zunzhe;Yu, Fangpu;Guo, Xiaobin;Su, Guohai;Zhang, Yun;Zhang, Meng;Zhang, Cheng
The developmental origin, anatomical location, and other factors contribute to aortic heterogeneity in a physiological state. On this basis, vascular diseases occur at different ratios based on position specificity, even with the same risk factor. However, the continuous intersegmental aortic profile has been rarely reported at the single-cell level. To reveal aortic heterogeneity, we identified 15 cell subtypes from five continuous aortic segments by marker genes and functional definitions. The EC1 subtype highly expressed Vcam1 and Scarb2 genes in the aortic arch, which were reported to be associated with atherosclerosis. The newly identified Fbn1+ fibroblasts were found highly expressed in thoracic segments. More importantly, vascular smooth muscle cells (VSMCs) demonstrated a novel composition in which VSMC 4 marked with the gene Malat1 were mainly distributed in the abdominal segment. Malat1 knockout reduced MMPs and inflammatory factor production induced by Ang II in smooth muscle cells, and the Malat1 inhibitor exerted preventive, inhibitory, and reversing effects on AngII-induced abdominal aortic aneurysm (AAA) in vivo revealed by a series of animal experiments. Single-cell analysis of AngII-induced AAA tissues treated with or without the inhibitor further clarified the key role of Malat1+VSMC in the occurrence and progression of AAA. In summary, segmental gene expression and cell subtype features in normal aorta associated with different vascular diseases might provide potential therapeutic targets.
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影响因子：
4.6
作者：
Lim WW;Corden B;Ng B;Vanezis K;D'Agostino G;Widjaja AA;Song WH;Xie C;Su L;Kwek XY;Tee NGZ;Dong J;Ko NSJ;Wang M;Pua CJ;Jamal MH;Soh B;Viswanathan S;Schafer S;Cook SA
通讯作者：
Cook SA
影响因子：
--
作者：
An, Sheng Jun;Liu, Pei;Fu, Jun Qiu
通讯作者：
Fu, Jun Qiu
影响因子：
3.7
作者：
Duggirala A;Delogu F;Angelini TG;Smith T;Caputo M;Rajakaruna C;Emanueli C
通讯作者：
Emanueli C
影响因子：
5.3
作者：
Biros, Erik;Moran, Corey S.;Golledge, Jonathan
通讯作者：
Golledge, Jonathan
影响因子：
8
作者：
Cardenas, Christian L. Lino;Kessinger, Chase W.;Lindsay, Mark E.
通讯作者：
Lindsay, Mark E.