Author + information
- Rena Watanabe,
- Yui Takahashi,
- Miho Kojima,
- Remina Shirai,
- Kengo Sato and
- Takuya Watanabe
Background: Tumor necrosis factor-stimulated gene-6 (TSG-6), an anti-inflammatory protein, was shown to be localized in the neointima of injury-induced rat arteries. However, the modulatory effect of TSG-6 on atherogenesis has not yet been reported.
Methods: We aimed to evaluate the atheroprotective effects of TSG-6 on human endothelial cells (HECs), human monocyte-derived macrophages (HMDMs), human aortic smooth muscle cells (HASMCs) in vitro, and aortic lesions in apolipoprotein E-deficient (ApoE-/-) mice, along with its expression levels in coronary lesions and plasma from patients with coronary artery disease (CAD).
Results: TSG-6 was abundantly expressed in HECs, HMDMs, and HASMCs in vitro. TSG-6 significantly suppressed cell proliferation and lipopolysaccharide-induced up-regulation of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular adhesion molecule-1 in HECs. TSG-6 significantly suppressed inflammatory M1 phenotype, and suppressed oxidized low-density lipoprotein-induced foam cell formation associated with down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in HMDMs. In HASMCs, TSG-6 significantly suppressed migration and proliferation, but increased collagen-1 and collagen-3 expressions. Four-week-infusion of TSG-6 into ApoE-/- mice significantly retarded the development of aortic atherosclerotic lesions with decreased vascular inflammation, monocyte/macrophage, and SMC contents and increased collagen fibers. In addition, it decreased peritoneal M1 macrophages with down-regulation of inflammatory molecules, and lowered plasma total cholesterol levels. In CAD patients, plasma TSG-6 levels were significantly increased and TSG-6 was highly expressed in the fibrous cap within coronary atherosclerotic plaques.
Conclusions: These results suggest that TSG-6 contributes to the prevention and stability of atherosclerotic plaques. Thus, TSG-6 may serve as a novel therapeutic target for CAD.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Cutting Edge Vascular Medicine
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1205-360
- 2017 American College of Cardiology Foundation