title: Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting vascular cells.
abstract: Angiotensin-converting enzyme 2 (ACE2) is a newly discovered homolog of ACE whose actions oppose those of angiotensin II (AngII). However, the underlying mechanisms by which ACE2 effectively suppresses early atherosclerotic lesions remain poorly understood. Here, we show, both in vitro and in vivo, that ACE2 inhibited the development of early atherosclerotic lesions by suppressing the growth of vascular smooth muscle cells (VSMCs) and improving endothelial function. In a relatively large cohort animal study (66 rabbits), aortic segments transfected by Ad-ACE2 showed significantly attenuated fatty streak formation, neointimal macrophage infiltration, and alleviation of impaired endothelial function. Segments also showed decreased expression of monocyte chemoattractant protein 1, lectin-like oxidized low-density lipoprotein receptor 1, and proliferating cell nuclear antigen, which led to the delayed onset of atherosclerotic lesions. At the cellular level, ACE2 significantly modulated AngII-induced growth and migration in human umbilical vein endothelial cells and VSMCs. The antiatherosclerotic effect of ACE2 involved down-regulation of the ERK-p38, JAK-STAT, and AngII-ROS-NF-kappaB signaling pathways and up-regulation of the PI3K-Akt pathway. These findings revealed the molecular mechanisms of the antiatherosclerotic activity of ACE2 and suggested that modulation of ACE2 could offer a therapeutic option for treating atherosclerosis.
authors.affiliation: Shandong University Qilu Hospital, Jinan, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Yu Xia
authors.initials: YX
authors.lastname: Zhao
authors.forename: Yue Hui
authors.initials: YH
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Bi Ping
authors.initials: BP
authors.lastname: Deng
authors.forename: Zhao Li
authors.initials: ZL
authors.lastname: Zhou
authors.forename: Shu Ying
authors.initials: SY
authors.lastname: Li
authors.forename: Xiao Ting
authors.initials: XT
authors.lastname: Lu
authors.forename: Li Li
authors.initials: LL
authors.lastname: Song
authors.forename: Xue Ming
authors.initials: XM
authors.lastname: Lei
authors.forename: Wen Bo
authors.initials: WB
authors.lastname: Tang
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Chun Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Huai Dong
authors.initials: HD
authors.lastname: Song
authors.forename: Chun Xi
authors.initials: CX
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Dong
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D050197:Atherosclerosis / Q000201:enzymology / Q000503:physiopathology*; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D008084:Lipoxygenase; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
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