Interventional Cardiology Journal Open Access

RGC-32 deficiency protects endothelial cell from inflammation and attenuates atherosclerosis

EuroSciCon Conference on Clinical Cardiology and Cardiovascular Disease

May 24-25, 2018 London, UK

Shiyou Chen, Xiao-Bing Cui, Jun-Na Luan, Kun Dong, Sisi Chen, Yongyi Wang and Wendy T Watford

University of Georgia, Athens, USA RenMin Hospital of Wuhan University (Hubei General Hospital), China Renji Hospital, Shanghai Jiaotong University, China

Posters & Accepted Abstracts: Interv Cardiol J

Abstract:

Atherosclerosis is a major cause of morbidity and mortality worldwide, but the underlying mechanisms are not fully understood. Recent studies have shown that response gene to complement 32 (RGC-32) is closely associated with atherosclerosis. Whether or not RGC-32 plays a functional role in atherosclerosis, however, remains to be determined. In the present study, we found that RGC-32 was significantly induced in endothelial cells (ECs) of atherosclerotic lesions from both Apo lipoprotein E-deficient (ApoE/-) mice and human patients. RGC-32 deficiency (Rgc32-/-) attenuated the high-fat diet-induced and spontaneously developed atherosclerotic lesions in ApoE-/- mice without affecting serum cholesterol concentration. It appeared that Rgc32-/- mainly decreased the macrophage accumulation without altering collagen and smooth muscle contents or macrophage proliferation in the lesions. In addition, transplantation of wild-type (WT) mouse bone marrow to lethal irradiated Rgc32-/- mice did not alter Rgc32 deficiency-caused reduction in lesion size and macrophage content, suggesting that RGC-32 in resident vascular cells, but not the macrophages, plays a critical role in the atherogenesis. Of importance, Rgc32-/- decreased the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in ECs both in vivo and in vitro, resulting in a decreased monocyte-EC interaction. Mechanistically, RGC-32 mediated TNF-α-induced ICAM-1 and VCAM-1 expression through nuclear factor (NF)-κB. RGC-32 appeared to directly interact with NF-κB and further facilitate NF-κB nuclear translocation and its binding to ICAM-1 and VCAM-1 promoters. Taken together, our data demonstrate that RGC-32 promotes atherosclerosis by facilitating monocyte-EC interaction, due to the induction of endothelial ICAM-1 and VCAM-1 expression through NF-κB signalling.
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