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

Exp Mol Pathol. 2016 Oct;101(2):221-230. doi: 10.1016/j.yexmp.2016.09.004. Epub 2016 Sep 13.

Abstract

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.

Keywords: Atherosclerosis; C5b-9; Endothelial cells; Migration; Proliferation; RGC-32.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aorta / metabolism
  • Aorta / pathology*
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology*
  • Blotting, Western
  • Cell Cycle Proteins / metabolism*
  • Cell Movement*
  • Cell Proliferation
  • Complement Membrane Attack Complex / metabolism*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mitosis
  • Muscle Proteins / metabolism*
  • Myocytes, Smooth Muscle / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Transcription, Genetic

Substances

  • Cell Cycle Proteins
  • Complement Membrane Attack Complex
  • Muscle Proteins
  • Nerve Tissue Proteins
  • RGCC protein, human