RRC ID 69705
著者 Nagel F, Schaefer AK, Gonçalves IF, Acar E, Oszwald A, Kaiser P, Kain R, Trescher K, Eilenberg WH, Brostjan C, Santer D, Kiss A, Podesser BK.
タイトル The expression and role of tenascin C in abdominal aortic aneurysm formation and progression.
ジャーナル Interact Cardiovasc Thorac Surg
Abstract OBJECTIVES:Up-regulation of tenascin C (TNC), a matricellular protein, produced mainly by vascular smooth muscle cells (VSMC), is associated with the progression and dilation of abdominal aortic aneurysms (AAA). The aims of this study were (i) to evaluate whether serum levels of TNC in patients with AAA patients correlate with aortic diameter and (ii) to clarify the role of TNC in formation and progression of AAA in a murine model.
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.
巻・号 34(5)
ページ 841-848
公開日 2022-5-2
DOI 10.1093/icvts/ivac018
PII 6524594
PMID 35137102
PMC PMC9070497
MeSH Animals Aorta, Abdominal Aortic Aneurysm, Abdominal* Disease Models, Animal Humans Mice Mice, Inbred C57BL Mice, Knockout Tenascin / metabolism
IF 1.675
リソース情報
実験動物マウス RBRC00007