Osteopontin null mice exhibited significantly less cardiac fibrosis (0.7%) compared to wild-type mice (8.0%, p<0.01) after three weeks of AngII infusion.
Does osteopontin deficiency prevent angiotensin II-induced cardiac fibrosis in mice?
Osteopontin deficiency attenuates angiotensin II-induced cardiac fibrosis and hypertrophy in mice, suggesting OPN mediates fibrosis via cellular adhesion and proliferation.
Tasa de eventos absoluta: 0.7% vs 8%
valor p: p=<0.01
OBJECTIVES: Osteopontin (OPN) is upregulated in left ventricular hypertrophy and is stimulated by angiotensin II (AngII). Our objective was to determine whether mice deficient in OPN would be protected from AngII-induced cardiac fibrosis. BACKGROUND: Interstitial fibrosis can lead to myocardial dysfunction and ultimately heart failure. Osteopontin activates integrins that regulate cell adhesion, migration, and growth, thus implicating OPN in the process of cardiac fibrosis. METHODS: Osteopontin null (OPN(-/-)) mice (n = 18) and wild-type controls (n = 20) were infused with AngII (2.5 or 3.0 microg/kg/min) for four days or three weeks via osmotic mini-pumps. Hearts were assessed morphometrically and histologically, including quantitative assessment of fibrosis via optical microscopic imaging analysis. Cardiac fibroblasts derived from these mice were evaluated for adhesion and proliferation. Cardiac transcript expression for cytokines, extracellular matrix (ECM), integrin, and atrial natriuretic peptide were assessed. RESULTS: Osteopontin(-/-) mice exhibited less cardiac fibrosis (0.7%) than wild-type mice (8.0%) (p < 0.01) and lowered heart/body weight ratios (0.10% vs. 0.23%) (p < 0.01) after three weeks of AngII infusion. Expression of transforming growth factor-beta, fibronectin, and collagen was not different between OPN(-/-) and wild-type mice, despite the decrease in ECM accumulation in the OPN(-/-) mice. Adhesion to ECM substrates decreased by 30% to 50% in cardiac fibroblasts of OPN(-/-) mice but was restored in OPN(-/-) cells by the addition of recombinant osteopontin. CONCLUSIONS: Osteopontin mediates cardiac fibrosis, probably through the modulation of cellular adhesion and proliferation. Because OPN is increased in cardiac hypertrophy and its lack attenuates fibrosis, understanding of OPN function is essential to extend our knowledge about molecular determinants of cardiac hypertrophy and failure.
Collins et al. (Fri,) conducted a other in Angiotensin II-induced cardiac fibrosis (n=38). Osteopontin deficiency (OPN(-/-)) vs. Wild-type controls was evaluated on Cardiac fibrosis (p=<0.01). Osteopontin null mice exhibited significantly less cardiac fibrosis (0.7%) compared to wild-type mice (8.0%, p<0.01) after three weeks of AngII infusion.