Exosome-Mediated Transfer of ACE (Angiotensin-Converting Enzyme) From Adventitial Fibroblasts of Spontaneously Hypertensive Rats Promotes Vascular Smooth Muscle Cell Migration. Issue 4 (October 2018)

• Record Type: Journal Article
• Authors: Tong, Ying; Ye, Chao; Ren, Xing-Sheng; Qiu, Yun; Zang, Ying-Hao; Xiong, Xiao-Qing; Wang, Jue-Jin; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing
• Is Part Of: Hypertension. Volume 72:Issue 4(2018:Oct.)
• Publication Date: 2018-10
• Subjects: captopril -- exosomes -- fibroblasts -- hypertension -- vascular remodeling; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.118.11375
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Migration of vascular smooth muscle cells (VSMCs) is pivotal for vascular remodeling in hypertension. Vascular adventitial fibroblasts (AFs) are important in the homeostasis of vascular structure. This study is designed to investigate the roles of AF exosomes (AFE) in VSMC migration and underling mechanism. Primary VSMCs and AFs were obtained from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. VSMC migration was evaluated with Boyden chamber assay and wound healing assay. AFE from WKY rats and SHR were isolated and identified. AFE from SHR promoted but AFE from WKY rats had no significant effect on VSMC migration. The effects of AFE on VSMC migration were prevented by an exosome inhibitor GW4869, an AT1 R (Ang II [angiotensin II] type 1 receptor) antagonist losartan, or an inhibitor of ACE (angiotensin-converting enzyme) captopril. ACE contents and activity were much higher in AFE from SHR than those from WKY rats. There were no significant difference in Ang II and AT1 R mRNA and protein levels between AFE from SHR and AFE from WKY rats. AFE from SHR increased Ang II and ACE contents and ACE activity in VSMCs of WKY rats and SHR. The changes of Ang II contents and ACE activity were prevented by captopril. ACE knockdown in AFs reduced ACE contents and activity in AFE from SHR and inhibited AFE-induced migration of VSMCs of WKY rats and those of SHR. These results indicate that exosomes from AFs of SHR transfer ACE to VSMCs, which increases Ang II levels and activates AT1 R in VSMCs and thereby promotes VSMC migration. Abstract : Supplemental Digital Content is available in the text.