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Cardiac‐specific expression of myostatin or an inhibitor of myostatin regulate heart size at baseline and in response to hypertrophic stimuli
Author(s) -
Morissette Michael R,
Xiao Chun Yang,
Rosenzweig Anthony
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.41
Subject(s) - myostatin , medicine , endocrinology , muscle hypertrophy , phenylephrine , cardiac function curve , genetically modified mouse , transgene , biology , chemistry , heart failure , gene , biochemistry , blood pressure
Previously we have shown that Myostatin (MSTN), an inhibitor of muscle growth, is upregulated in cardiac hypertrophy and inhibits cardiomyocyte growth in vitro . Our objective was to determine the in vivo role of MSTN in cardiac hypertrophy. To do this we generated cardiac‐specific transgenic mouse lines (TG) that express MSTN and the inhibitory propeptide (dnMSTN). Heart weight/tibial length of MSTN TG was decreased 6.2±1.35% (p<0.01, n=13) vs non‐transgenic mice (NTG), while dnMSTN TG showed a 13.6±1.31% (p<0.001, n=35) increase, associated with increased p38 phosphorylation. To determine the effect of MSTN inhibition in hypertrophy we subjected dnMSTN TG to trans‐aortic constriction (TAC), swimming, and phenylephrine (PE) infusion for 14 days. TAC produced similar growth between NTG (32.9±0.97%, p<0.01, n=7) and dnMSTN TG (35.6±5.9%, p<0.01, n=7) however further growth in swum and PE‐treated dnMSTN TG was absent, suggesting stimulus‐specific modulation of hypertrophy by MSTN. Echocardiography revealed normal function in both TG lines. Interestingly skeletal muscle mass was increased 12.9±0.83% (p<0.001, n=28) in dnMSTN TG, and decreased (16.6±0.83%, p<0.001, n=6) in MSTN TG. Immunoprecipitation of the dnMSTN and MSTN transgene proteins revealed their presence in the circulation. We conclude that MSTN is a negative regulator of cardiac growth. Support: NHLBI [AR], and NIA, AHA [MRM].