Continuous activation of gp130 in double-transgenic mice overexpressing IL-6 and IL-6R caused ventricular myocardial hypertrophy, increasing the heart-to-body weight ratio to 0.66% compared to 0.51% in controls (p<0.05).
Tasa de eventos absoluta: 0.66% vs 0.51%
valor p: p=<0.05
To investigate the physiological roles of gp130 in detail and to determine the pathological consequence of abnormal activation of gp130, transgenic mice having continuously activated gp130 were created. This was carried out by mating mice from interleukin 6 (IL-6) and IL-6 receptor (IL-6R) transgenic lines. Offspring overexpressing both IL-6 and IL-6R showed constitutive tyrosine phosphorylation of gp130 and a downstream signaling molecule, acute phase response factor/signal transducer and activator of transcription 3. Surprisingly, the distinguishing feature of such offspring was hypertrophy of ventricular myocardium and consequent thickened ventricular walls of the heart, where gp130 is also expressed, in adulthood. Transgenic mice overexpressing either IL-6 or IL-6R alone did not show detectable myocardial abnormalities. Neonatal heart muscle cells from normal mice, when cultured in vitro, enlarged in response to a combination of IL-6 and a soluble form of IL-6R. The results suggest that activation of the gp130 signaling pathways leads to cardiac hypertrophy and that these signals might be involved in physiological regulation of myocardium.
Hirota et al. (Tue,) conducted a other in Myocardial hypertrophy. Overexpression of IL-6 and IL-6R (Double-transgenic) vs. Single transgenic or non-transgenic mice was evaluated on Ratio of heart weight to body weight (%) (p=<0.05). Continuous activation of gp130 in double-transgenic mice overexpressing IL-6 and IL-6R caused ventricular myocardial hypertrophy, increasing the heart-to-body weight ratio to 0.66% compared to 0.51% in controls (p<0.05).