RGC-32 is expressed in the human atherosclerotic arterial wall: Role in C5b-9-induced cell proliferation and migration.
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.
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA; Department of Internal Medicine, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Sonia I
SI
Vlaicu
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA; Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA.
Alexandru
A
Tatomir
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA.
Dallas
D
Boodhoo
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA.
Takahiro
T
Ito
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA.
Matthew
M
Fosbrink
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA.
Cornelia
C
Cudrici
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA; Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA.
Armugam P
AP
Mekala
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA.
Jonathan
J
Ciriello
Department of Pathology, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Doiniţa
D
Crişan
Department of Pathology, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Emil
E
Boţan
Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Violeta
V
Rus
Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, USA; Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA. Electronic address: hrus@umaryland.edu.
Horea
H
Rus
D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009124:Muscle Proteins / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D015938:Complement Membrane Attack Complex; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human
Atherosclerosis; C5b-9; Endothelial cells; Migration; Proliferation; RGC-32