Overexpression of integrin α11 induces cardiac fibrosis in mice

A Romaine, I W Sørensen, C Zeltz, N Lu, P M Erusappan, A O Melleby, L Zhang, B Bendiksen, E L Robinson, J M Aronsen, K M Herum, H E Danielsen, I Sjaastad, G Christensen, D Gullberg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


AIM: To understand the role of the collagen-binding integrin α11 in vivo, we have used a classical approach of creating a mouse strain overexpressing integrin α11. A transgenic mouse strain overexpressing α11 in muscle tissues was analysed in the current study with special reference to the heart tissue.

METHODS: We generated and phenotyped integrin α11 transgenic (TG) mice by echocardiography, magnetic resonance imaging and histology. Wild-type (WT) mice were subjected to aortic banding (AB) and the expression of integrin α11 was measured in flow cytometry-sorted cardiomyocytes and non-myocytes.

RESULTS: TG mice developed left ventricular concentric hypertrophy by 6 months, with increased collagen deposition and reactivation of mRNA encoding foetal genes associated with cardiovascular pathological remodelling compared to WT mice. Masson's trichrome staining revealed interstitial fibrosis, confirmed additionally by magnetic resonance imaging and was found to be most prominent in the cardiac septum of TG but not WT mice. TG hearts expressed increased levels of transforming growth factor-β2 and transforming growth factor-β3 and upregulated smooth muscle actin. Macrophage infiltration coincided with increased NF-κB signalling in TG but not WT hearts. Integrin α11 expression was increased in both cardiomyocytes and non-myocyte cells from WT AB hearts compared to sham-operated animals.

CONCLUSION: We report for the first time that overexpression of integrin α11 induces cardiac fibrosis and left ventricular hypertrophy. This is a result of changes in intracellular hypertrophic signalling and secretion of soluble factors that increase collagen production in the heart.

Original languageEnglish
Article numbere13025
JournalActa Physiologica
Issue number2
Publication statusPublished - Feb 2018
Externally publishedYes


  • Animals
  • Fibrosis
  • Hypertrophy, Left Ventricular/metabolism
  • Integrin alpha Chains/metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Myocardium/metabolism

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