TY - JOUR
T1 - Cardiac-specific LIM protein FHL2 modifies the hypertrophic response to β-adrenergic stimulation
AU - Kong, Yanfeng
AU - Shelton, John M.
AU - Rothermel, Beverly
AU - Li, Xiangqing
AU - Richardson, James A.
AU - Bassel-Duby, Rhonda
AU - Williams, R. Sanders
PY - 2001/6/5
Y1 - 2001/6/5
N2 - Background - A deficiency of muscle LIM protein results in dilated cardiomyopathy, but the function of other LIM proteins in the heart has not been assessed previously. We have characterized the expression and function of FHL2, a heart-specific member of the LIM domain gene family. Methods and Results - Expression of FHL2 mRNA and protein was examined by Northern blot, in situ hybridization, and Western blot analyses of fetal and adult mice. FHL2 transcripts are present at embryonic day (E) 7.5 within the cardiac crescent in a pattern that resembles that of Nkx2.5 mRNA. During later stages of cardiac development and in adult animals, FHL2 expression is localized to the myocardium and absent from endocardium, cardiac cushion, outflow tract, or coronary vasculature. The gene encoding FHL2 was disrupted by homologous recombination, and knockout mice devoid of FHL2 were found to undergo normal cardiovascular development. In the absence of FHL2, however, cardiac hypertrophy resulting from chronic infusion of isoproterenol is exaggerated (59% versus 20% increase in heart weight/body weight in FHL null versus wild-type mice; P<0.01). Conclusions - FHL2 is an early marker of cardiogenic cells and a cardiac-specific LIM protein in the adult. FHL2 is not required for normal cardiac development but modifies the hypertrophic response to β-adrenergic stimulation.
AB - Background - A deficiency of muscle LIM protein results in dilated cardiomyopathy, but the function of other LIM proteins in the heart has not been assessed previously. We have characterized the expression and function of FHL2, a heart-specific member of the LIM domain gene family. Methods and Results - Expression of FHL2 mRNA and protein was examined by Northern blot, in situ hybridization, and Western blot analyses of fetal and adult mice. FHL2 transcripts are present at embryonic day (E) 7.5 within the cardiac crescent in a pattern that resembles that of Nkx2.5 mRNA. During later stages of cardiac development and in adult animals, FHL2 expression is localized to the myocardium and absent from endocardium, cardiac cushion, outflow tract, or coronary vasculature. The gene encoding FHL2 was disrupted by homologous recombination, and knockout mice devoid of FHL2 were found to undergo normal cardiovascular development. In the absence of FHL2, however, cardiac hypertrophy resulting from chronic infusion of isoproterenol is exaggerated (59% versus 20% increase in heart weight/body weight in FHL null versus wild-type mice; P<0.01). Conclusions - FHL2 is an early marker of cardiogenic cells and a cardiac-specific LIM protein in the adult. FHL2 is not required for normal cardiac development but modifies the hypertrophic response to β-adrenergic stimulation.
KW - Genetics
KW - Hypertrophy
KW - Molecular biology
KW - Myocardium
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U2 - 10.1161/01.CIR.103.22.2731
DO - 10.1161/01.CIR.103.22.2731
M3 - Article
C2 - 11390345
AN - SCOPUS:0035811023
SN - 0009-7322
VL - 103
SP - 2731
EP - 2738
JO - Circulation
JF - Circulation
IS - 22
ER -