期刊
ACTA BIOMATERIALIA
卷 6, 期 1, 页码 170-178出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2009.06.006
关键词
Hyaluronan oligomers; Tumor necrosis factor alpha; Transforming growth factor-beta 1; Elastin matrix regeneration; Aortic aneurysm
资金
- American Heart Association [SDG 0335085N]
- National Institutes of Health [C06RR018823, EB006078-01A1, HL092051-01A1]
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR018823] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL092051] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R21EB006078] Funding Source: NIH RePORTER
Elastin breakdown in vascular aneurysms is mediated by cytokines such as tumor necrosis factor alpha (TNF-alpha, which induces vascular smooth muscle cell (SMC) activation and regulates their deposition of matrix. We previously demonstrated that exogenous supplementation with TGF-beta 1 (1 ng ml(-1)) and hyaluronan oligomers (0.786 kDa, 0.2 mu g ml(-1)) cues the upregulation of elastin matrix synthesis by healthy cultured SMCs. Here, we determine whether these cues likewise enhance elastin matrix synthesis and assembly by TNF-alpha-stimulated SMCs, while restoring their healthy phenotype. Adult rat aortic SMCs were treated with TNF-alpha alone or together with TGF-beta 1/hyaluronan oligomeric cues and the release of inflammatory markers were monitored during over a 21 day culture. Biochemical analysis was used to quantify cell proliferation, matrix protein synthesis and cross-linking efficiency, while immunofluorescence and electron microscopy were used to analyze the elastin matrix quality. It was observed that SMC activation with TNF-alpha (10 ng ml(-1)) induced matrix calcification and promoted production of elastolytic MMP-2 and MMP-9. However, these effects were attenuated by the addition of TGF-beta 1 and HA oligomer cues to TNF-alpha-stimulated cultures, which also enhanced tropoelastin and collagen production, improved elastin matrix yield and cross-linking, promoted elastin fiber formation and suppressed elastase activity, although the release of MMP-2 and MMP-9 was not affected. Overall, the results suggest that TGF-beta 1 and HA oligomers are potentially useful in suppressing SMC activation and inducing regenerative elastin repair within aneurysms. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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