Xiao-Bing Cui1, Jun-Na Luan1, Kun Dong1, Sisi Chen1, Yongyi Wang1, Wendy T Watford1, Shi-You Chen2. 1. From the Department of Physiology and Pharmacology (X.-B.C., J.-N.L., K.D., S.C., S.-Y.C.) and Department of Infectious Diseases (W.T.W.), University of Georgia, Athens; Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, China (S.C., S.-Y.C.); and Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China (Y.W.). 2. From the Department of Physiology and Pharmacology (X.-B.C., J.-N.L., K.D., S.C., S.-Y.C.) and Department of Infectious Diseases (W.T.W.), University of Georgia, Athens; Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, China (S.C., S.-Y.C.); and Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China (Y.W.). sc229@uga.edu.
Abstract
OBJECTIVE: The objective of this study is to determine the role and underlying mechanisms of RGC-32 (response gene to complement 32 protein) in atherogenesis. APPROACH AND RESULTS: RGC-32 was mainly expressed in endothelial cells of atherosclerotic lesions in both ApoE-/- (apolipoprotein E deficient) 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. Rgc32-/- seemed to decrease the macrophage content without altering collagen and smooth muscle contents or lesional macrophage proliferation in the lesions. Transplantation of WT (wild type) mouse bone marrow to lethally irradiated Rgc32-/- mice did not alter Rgc32-/--caused reduction of lesion formation and macrophage accumulation, 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 ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) in endothelial cells both in vivo and in vitro, resulting in a decrease in TNF-α (tumor necrosis factor-α)-induced monocyte-endothelial cell interaction. Mechanistically, RGC-32 mediated the ICAM-1 and VCAM-1 expression, at least partially, through NF (nuclear factor)-κB signaling pathway. RGC-32 directly interacted with NF-κB and facilitated its nuclear translocation and enhanced TNF-α-induced NF-κB binding to ICAM-1 and VCAM-1 promoters. CONCLUSIONS: RGC-32 mediates atherogenesis by facilitating monocyte-endothelial cell interaction via the induction of endothelial ICAM-1 and VCAM-1 expression, at least partially, through NF-κB signaling pathway.
OBJECTIVE: The objective of this study is to determine the role and underlying mechanisms of RGC-32 (response gene to complement 32 protein) in atherogenesis. APPROACH AND RESULTS: RGC-32 was mainly expressed in endothelial cells of atherosclerotic lesions in both ApoE-/- (apolipoprotein E deficient) 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. Rgc32-/- seemed to decrease the macrophage content without altering collagen and smooth muscle contents or lesional macrophage proliferation in the lesions. Transplantation of WT (wild type) mouse bone marrow to lethally irradiated Rgc32-/- mice did not alter Rgc32-/--caused reduction of lesion formation and macrophage accumulation, 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 ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) in endothelial cells both in vivo and in vitro, resulting in a decrease in TNF-α (tumor necrosis factor-α)-induced monocyte-endothelial cell interaction. Mechanistically, RGC-32 mediated the ICAM-1 and VCAM-1 expression, at least partially, through NF (nuclear factor)-κB signaling pathway. RGC-32 directly interacted with NF-κB and facilitated its nuclear translocation and enhanced TNF-α-induced NF-κB binding to ICAM-1 and VCAM-1 promoters. CONCLUSIONS: RGC-32 mediates atherogenesis by facilitating monocyte-endothelial cell interaction via the induction of endothelial ICAM-1 and VCAM-1 expression, at least partially, through NF-κB signaling pathway.
Authors: Alan Daugherty; Alan R Tall; Mat J A P Daemen; Erling Falk; Edward A Fisher; Guillermo García-Cardeña; Aldons J Lusis; A Phillip Owens; Michael E Rosenfeld; Renu Virmani Journal: Arterioscler Thromb Vasc Biol Date: 2017-07-20 Impact factor: 8.311
Authors: Ralph Gareus; Elena Kotsaki; Sofia Xanthoulea; Ingeborg van der Made; Marion J J Gijbels; Rozina Kardakaris; Apostolos Polykratis; George Kollias; Menno P J de Winther; Manolis Pasparakis Journal: Cell Metab Date: 2008-11 Impact factor: 27.287
Authors: Jun-Ming Tang; Ning Shi; Kun Dong; Scott A Brown; Amanda E Coleman; Matthew A Boegehold; Shi-You Chen Journal: Circ Res Date: 2018-10-12 Impact factor: 17.367
Authors: Hong S Lu; Ann Marie Schmidt; Robert A Hegele; Nigel Mackman; Daniel J Rader; Christian Weber; Alan Daugherty Journal: Arterioscler Thromb Vasc Biol Date: 2019-12-23 Impact factor: 8.311
Authors: Andrew P Voigt; Nathaniel K Mullin; Edwin M Stone; Budd A Tucker; Todd E Scheetz; Robert F Mullins Journal: Prog Retin Eye Res Date: 2020-12-28 Impact factor: 19.704