| First Author | Romaine A | Year | 2018 |
| Journal | Acta Physiol (Oxf) | Volume | 222 |
| Issue | 2 | PubMed ID | 28771943 |
| Mgi Jnum | J:278252 | Mgi Id | MGI:6323317 |
| Doi | 10.1111/apha.12932 | Citation | Romaine A, et al. (2018) Overexpression of integrin alpha11 induces cardiac fibrosis in mice. Acta Physiol (Oxf) 222(2) |
| abstractText | AIM: To understand the role of the collagen-binding integrin alpha11 in vivo, we have used a classical approach of creating a mouse strain overexpressing integrin alpha11. A transgenic mouse strain overexpressing alpha11 in muscle tissues was analysed in the current study with special reference to the heart tissue. METHODS: We generated and phenotyped integrin alpha11 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 alpha11 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-beta2 and transforming growth factor-beta3 and upregulated smooth muscle actin. Macrophage infiltration coincided with increased NF-kappaB signalling in TG but not WT hearts. Integrin alpha11 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 alpha11 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. |
