Suppressor of cytokine signaling 3 is a negative regulator for neointimal hyperplasia of vein graft stenosis.

Abstract

Coronary artery bypass graft (CABG) surgery is one of the most effective treatments for coronary artery disease. However, neointimal hyperplasia and ultimate luminal occlusion that is caused by vascular smooth muscle cell (VSMC) migration, proliferation and inflammatory response impede the long-term prognosis. The SOCS3 protein is involved in modulating various autoimmune and inflammatory diseases. However, the role of SOCS3 in vein graft disease is still unclear. We found that the mRNA and protein expression levels of IL-1β, IL-6, MCP-1, ICAM-1, TNF-α, STAT3, P-STAT3 and SOCS3 were significantly higher in the graft samples compared to normal veins. After transfecting the recombinant adenovirus carrying the rat SOCS3 gene into cultured rat VSMCs or grafting veins in rat, SOCS3 overexpression was found to significantly inhibit VSMC migration and proliferation in vitro and neointimal hyperplasia in vivo, respectively. Furthermore, SOCS3 overexpression inhibited VSMC migration and growth in vitro and alleviated VSMC inflammation in vitro by inhibiting STAT3 activation and phosphorylation. In conclusion, SOCS3 is a crucial physiological negative regulator for vein graft failure and provides a novel target for vein graft stenosis therapy after CABG.

• Authors: Shui Xiang, Jinping Liu, Nianguo Dong, Jiawei Shi, Yaqiong Xiao, Yu Wang, Xingjian Hu, Li Gong, Wenshuo Wang
• Journal: Journal of vascular research (J Vasc Res) Vol. 51 Issue 2 Pg. 132-43 ( 2014) ISSN: 1423-0135 [Electronic] Switzerland
• PMID: 24685947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Inflammation Mediators
• STAT3 Transcription Factor
• Socs3 protein, rat
• Stat3 protein, rat
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins

Topics

• Animals
• Carotid Arteries (surgery)
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Cytokines (metabolism)
• Disease Models, Animal
• Graft Occlusion, Vascular (etiology, metabolism, pathology, prevention & control)
• Hyperplasia
• Inflammation Mediators (metabolism)
• Jugular Veins (metabolism, pathology, transplantation)
• Male
• Muscle, Smooth, Vascular (metabolism, pathology)
• Myocytes, Smooth Muscle (metabolism, pathology)
• Neointima
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins (genetics, metabolism)
• Time Factors
• Transfection
• Vascular Grafting (adverse effects)