The expression and role of tenascin C in abdominal aortic aneurysm formation and progression

肌腱蛋白C在腹主动脉瘤形成和进展中的表达及作用

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作者:Felix Nagel, Anne-Kristin Schaefer, Inês Fonseca Gonçalves, Eylem Acar, Andre Oszwald, Philipp Kaiser, Renate Kain, Karola Trescher, Wolf H Eilenberg, Christine Brostjan, David Santer, Attila Kiss, Bruno K Podesser

Conclusions

TNC might play a causative role in the formation, dilation and progression of AAA. Our results indicate that TNC might be a biomarker as well as a potential therapeutic target in the treatment of AAA.

Methods

In 15 patients with AAA serum levels of TNC were measured and correlated with aortic diameters. Moreover, in a murine calcium chloride AAA model, the impact of TNC deficiency on AAA diameter was evaluated. Finally, human VSMC were incubated with TNC to clarify its regulating potential.

Results

In the clinical cohort, there was a trend of correlation between serum TNC levels and AAA diameter (P = 0.055). TNC knock out mice with AAA showed significantly lower diameter ratios compared to the wild-type group (WT) 3 weeks (P < 0.05) and 10 weeks (P < 0.05) after AAA induction. Immunohistochemistry revealed increased TNC expression in aortic tissue from WT with AAA as compared sham-operated mice. Furthermore, WT with AAA showed a more disrupted Elastin structure than TNC knock out mice 10 weeks after AAA induction. In human aortic VSMC, TNC incubation induced expression of remodelling associated proteins. Conclusions: TNC might play a causative role in the formation, dilation and progression of AAA. Our results indicate that TNC might be a biomarker as well as a potential therapeutic target in the treatment of AAA.

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