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

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

Research output: Journal article (peer-reviewed)Journal article

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)841-848
Number of pages8
JournalInteractive Cardiovascular and Thoracic Surgery
Volume34
Issue number5
DOIs
Publication statusPublished - 1 May 2022

Keywords

  • Animals
  • Aorta, Abdominal
  • Aortic Aneurysm, Abdominal
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Tenascin/metabolism
  • Serum marker
  • Tenascin C
  • Abdominal aortic aneurysm
  • Extracellular matrix

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

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