The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding-Debanding of the Ascending Aorta

Mireia Perera-Gonzalez, Attila Kiss, Philipp Kaiser, Michael Holzweber, Felix Nagel, Simon Watzinger, Eylem Acar, Petra Lujza Szabo, Inês Fonseca Gonçalves, Lukas Weber, Patrick Michael Pilz, Lubos Budinsky, Thomas Helbich, Bruno Karl Podesser

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

7 Citations (Scopus)

Abstract

BACKGROUND: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown.

METHODS: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment.

RESULTS: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression; however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1.

CONCLUSIONS: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (α-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics.

Original languageEnglish
Article number2023
Pages (from-to)1-14
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume22
Issue number4
DOIs
Publication statusPublished - 2 Feb 2021

Keywords

  • Animals
  • Aorta/physiology
  • Atrial Natriuretic Factor/genetics
  • Collagen Type I/genetics
  • Constriction, Pathologic
  • Fibroblasts/metabolism
  • Heart Ventricles/metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Knockout
  • Peptidyl-Dipeptidase A/metabolism
  • RNA, Messenger/genetics
  • Stroke Volume
  • Tenascin/metabolism
  • Ventricular Function
  • Ventricular Remodeling

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