gp130 plays a critical role in pressure overload-induced cardiac hypertrophy

gp130, a common receptor for the interleukin 6 family, plays pivotal roles in growth and survival of cardiac myocytes. In the present study, we examin ed the role of gp130 in pressure overload-induced cardiac hypertrophy using transgenic (TG) mice, which express a dominant negative mutant of gp130 in the heart under the control of a myosin heavy chain promoter. TG mice were apparently healthy and fertile. There were no differences in body weight a nd heart weight between TG mice and littermate wild type (WT) mice. Pressur e overload-induced increases in the heart weight/body weight ratio, ventric ular wall thickness, and cross-sectional areas of cardiac myocytes were sig nificantly smaller in TG mice than in WT mice, Northern blot analysis revea led that pressure overload-induced up-regulation of brain natriuretic facto r gene and down regulation of sarcoplasmic reticulum Ca2+ ATPase 2 gene wer e attenuated in TG mice. Pressure overload activated ERKs and STAT3 in the heart of WT mice, whereas pressure overload-induced activation of STAT3, bu t not of ERKs, was suppressed in TG mice. These results suggest that gp130 plays a critical role in pressure overload-induced cardiac hypertrophy poss ibly through the STAT3 pathway.