RGC-32 is expressed in the human atherosclerotic arterial wall: Role in C5b-9-induced cell proliferation and migration

• RGC-32 is expressed in human aortic atherosclerotic wall.
• RGC-32 expression increases with the progression of atherosclerosis.
• C5b-9 induced HAEC proliferation and migration rely on RGC-32 expression.
• Silencing RGC-32 in HAEC impacts on genes involved in cell adhesion and cell cycle.
• RGC-32 regulates HAEC migration through the regulation of ROCK1.

The complement system is an important player in the development of atherosclerosis. Previously reported as a cell cycle regulator, RGC-32 is an essential effector of the terminal complement complex, C5b-9. In this study, our aims were to determine the expression of RGC-32 in the human atherosclerotic arterial wall and to delineate the mechanisms through which RGC-32 affects C5b-9-induced endothelial cell proliferation and migration. We now demonstrate that RGC-32 is expressed in human aortic atherosclerotic wall and that RGC-32 expression increases with the progression of atherosclerosis. Furthermore, silencing of RGC-32 expression abolished C5b-9-induced human aortic endothelial cell (HAEC) proliferation and migration. Of the 279 genes differentially expressed in HAECs after RGC-32 silencing, the genes involved in cell adhesion and cell cycle activation were significantly regulated by RGC-32. RGC-32 silencing caused a significant reduction in the expression of cyclin D1, cyclin D3, Akt, ROCK1, Rho GDP dissociation inhibitor alpha and profilin. These data suggest that RGC-32 mediates HAEC migration through the regulation of RhoA and ROCK1 expression and is involved in actin cytoskeletal organization. Thus, RGC-32 has promising therapeutic potential with regard to angiogenesis and atherosclerosis.

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