Response gene to complement 32 promotes vascular lesion formation through stimulation of smooth muscle cell proliferation and migration.

Abstract

OBJECTIVE:

The objectives of this study were to determine the role of response gene to complement 32 (RGC-32) in vascular lesion formation after experimental angioplasty and to explore the underlying mechanisms.

METHODS AND RESULTS:

Using a rat carotid artery balloon-injury model, we documented for the first time that neointima formation was closely associated with a significantly increased expression of RGC-32 protein. Short hairpin RNA knockdown of RGC-32 via adenovirus-mediated gene delivery dramatically inhibited the lesion formation by 62% as compared with control groups 14 days after injury. Conversely, RGC-32 overexpression significantly promoted the neointima formation by 33%. Gain- and loss-of-function studies in primary culture of rat aortic smooth muscle cells (RASMCs) indicated that RGC-32 is essential for both the proliferation and migration of RASMCs. RGC-32 induced RASMC proliferation by enhancing p34(CDC2) activity. RGC-32 stimulated the migration of RASMC by inducing focal adhesion contact and stress fiber formation. These effects were caused by the enhanced rho kinase II-α activity due to RGC-32-induced downregulation of Rad GTPase.

CONCLUSIONS:

RGC-32 plays an important role in vascular lesion formation following vascular injury. Increased RGC-32 expression in vascular injury appears to be a novel mechanism underlying the migration and proliferation of vascular smooth muscle cells. Therefore, targeting RGC-32 is a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases.

• Authors: Jia-Ning Wang, Ning Shi, Wei-Bing Xie, Xia Guo, Shi-You Chen
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 31 Issue 8 Pg. e19-26 (Aug 2011) ISSN: 1524-4636 [Electronic] United States
• PMID: 21636805 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cell Cycle Proteins
• Muscle Proteins
• Nerve Tissue Proteins
• RNA, Small Interfering
• Rgcc protein, rat
• Rrad protein, rat
• ras Proteins

Topics

• Animals
• Base Sequence
• Carotid Artery Injuries (etiology, genetics, pathology, physiopathology)
• Cell Cycle Proteins (antagonists & inhibitors, genetics, physiology)
• Cell Movement (genetics, physiology)
• Cell Proliferation
• Cells, Cultured
• Gene Expression
• Gene Knockdown Techniques
• Male
• Muscle Proteins (antagonists & inhibitors, genetics, physiology)
• Myocytes, Smooth Muscle (pathology, physiology)
• Neointima (pathology, physiopathology)
• Nerve Tissue Proteins (antagonists & inhibitors, genetics, physiology)
• RNA, Small Interfering (genetics)
• Rats
• Rats, Sprague-Dawley
• ras Proteins (genetics, physiology)