Introduction - TGF-β1 plays a key role in the hypertension-associated cardiac fibrosis by acting on cardiac fibroblast differentiation to produce α-smooth muscle actin (α-SMA)-expressing myofibroblasts. Integrin-mediated mechanotransduction induces TGF-β1 activation via its release from latent TGF-β1 binding protein-1 (LTBP-1). Integrin αvβ5 is expressed in the heart tissue and is known to be involved in the TGF-β1 activation. Purpose: We tested if the hypertensive stimuli present in a rat model of hypertension were sufficient to elicit TGF-β1 activation by integrin αvβ5-mediated traction. Methods: Immunohistochemistry and Western blot analyses were conducted on heart tissue from Spontaneously Hypertensive Rats (SHR, n=10) and normotensive Wistar Kyoto rats (WKY, n=10). Results: SHR heart tissue displayed a greater amount of ECM deposition particularly in the perivascular region. Integrin αvβ5 (Figure 1a-c) and LTBP-1 expression (Figure 1g-i) were also significantly increased in the SHR heart (p<0.05). Moreover, isolated SHR cardiac fibroblasts (± recombinant TGF-β1) were more prone to switch to α-SMA expressing cells in vitro, compared to normotensive cardiac fibroblasts, and had a statistically significant higher expression of integrin αvβ5 and LTBP-1 (p<0.05, Figure 1f,n). Conclusions: Hypertension stimulated the upregulation of integrin αvβ5, LTBP-1, α-SMA and TGF-β1. It also promoted ECM deposition, the main defining feature of cardiac fibrosis. These results open future studies on molecular tools targeting integrins in cardiac fibroblasts as a strategy to selectively block integrin-mediated TGF-β1 activation and reduce the progression of the cardiac fibrosis process.
Differentiation of fibroblasts into myofibroblasts during hypertensive-derived cardiac fibrosis is promoted by alpha-v beta-5 integrin-mediated activation of TGF-beta1 / G.L. Perrucci, D. Tosi, P. Nigro, G. Bulfamante, F. Magrini, G. Pompilio, F. Lombardi. - In: EUROPEAN HEART JOURNAL. - ISSN 0195-668X. - 36:suppl.(2015 Aug 31), pp. 833-833. ((Intervento presentato al convegno ESC tenutosi a London nel 2015.
|Titolo:||Differentiation of fibroblasts into myofibroblasts during hypertensive-derived cardiac fibrosis is promoted by alpha-v beta-5 integrin-mediated activation of TGF-beta1|
PERRUCCI, GIANLUCA LORENZO (Primo)
POMPILIO, GIULIO (Penultimo)
LOMBARDI, FEDERICO (Ultimo)
|Parole Chiave:||Hypertension; Integrins; Cardiac fibrosis|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||31-ago-2015|
|Appare nelle tipologie:||01 - Articolo su periodico|