Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.
Fatty acid binding protein 4 (FABP4) is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG) mice using α myosin-heavy chain (α-MHC) promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC) procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Ji
J
Zhang
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Congzhen
C
Qiao
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Lin
L
Chang
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Yanhong
Y
Guo
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Yanbo
Y
Fan
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Luis
L
Villacorta
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Y Eugene
YE
Chen
Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
Jifeng
J
Zhang
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D011312:Pressure; D051381:Rats; D015854:Up-Regulation
C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma