TY - JOUR
T1 - Adiponectin protects against the development of systolic dysfunction following myocardial infarction
AU - Shibata, Rei
AU - Izumiya, Yasuhiro
AU - Sato, Kaori
AU - Papanicolaou, Kyriakos
AU - Kihara, Shinji
AU - Colucci, Wilson S.
AU - Sam, Flora
AU - Ouchi, Noriyuki
AU - Walsh, Kenneth
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (HL86785, AG15052, HL77774, and HL81587) to K.W. R.S. was supported by grants from the American Heart Association Postdoctoral Fellowship Award, Northeast Affiliate. Y.I. was supported by grants from the American Heart Association Postdoctoral Fellowship Award, Northeast Affiliate. N.O. was supported by a Department of Medicine Pilot Project Grant from Boston University and American Heart Association Scientist Development Grant, Northeast Affiliate.
PY - 2007/6
Y1 - 2007/6
N2 - There is an association between obesity and heart failure associated with LV dysfunction. Adiponectin is an adipocyte-derived hormone that is downregulated in obesity. Here, we examined the role of adiponectin in cardiac remodeling after myocardial infarction with loss- and gain-of-function genetic manipulations in an experimental model. Myocardial infarction was created in adiponectin-deficient (APN-KO) and wild-type (WT) mice by the permanent ligation of the left anterior descending (LAD) artery. For some experiments, adenoviral vectors expressing adiponectin or β-galactosidase were delivered systemically. Cardiac structure and function were assessed by echocardiographic and Millar catheter measurements. Myocardial capillary density was assessed by staining with anti-CD31 antibody. Myocyte apoptotic activity was determined by TUNEL-staining. Myocardial interstitial fibrosis was evaluated by Masson's trichrome staining. APN-KO mice showed exacerbated left ventricular (LV) dilation, myocyte hypertrophy and contractile dysfunction compared with WT mice at 4 weeks after LAD ligation. Impaired LV function in APN-KO mice was coupled to myocyte hypertrophy, increased apoptotic activity and interstitial fibrosis in the remote zone, and reduced capillary density in the infarct border zone. No difference in infarct size was observed between WT and APN-KO mice. Administration of adenovirus-mediated adiponectin in WT mice resulted in decreased LV dilatation and improved LV function that was associated with increased capillary density in the infarct border zone and decreased myocyte hypertrophy, diminished myocardial apoptosis and decreased interstitial fibrosis in the remote zone. These data suggest that adiponectin protects against the development of systolic dysfunction after myocardial infarction through its abilities to suppress cardiac hypertrophy and interstitial fibrosis, and protect against myocyte and capillary loss.
AB - There is an association between obesity and heart failure associated with LV dysfunction. Adiponectin is an adipocyte-derived hormone that is downregulated in obesity. Here, we examined the role of adiponectin in cardiac remodeling after myocardial infarction with loss- and gain-of-function genetic manipulations in an experimental model. Myocardial infarction was created in adiponectin-deficient (APN-KO) and wild-type (WT) mice by the permanent ligation of the left anterior descending (LAD) artery. For some experiments, adenoviral vectors expressing adiponectin or β-galactosidase were delivered systemically. Cardiac structure and function were assessed by echocardiographic and Millar catheter measurements. Myocardial capillary density was assessed by staining with anti-CD31 antibody. Myocyte apoptotic activity was determined by TUNEL-staining. Myocardial interstitial fibrosis was evaluated by Masson's trichrome staining. APN-KO mice showed exacerbated left ventricular (LV) dilation, myocyte hypertrophy and contractile dysfunction compared with WT mice at 4 weeks after LAD ligation. Impaired LV function in APN-KO mice was coupled to myocyte hypertrophy, increased apoptotic activity and interstitial fibrosis in the remote zone, and reduced capillary density in the infarct border zone. No difference in infarct size was observed between WT and APN-KO mice. Administration of adenovirus-mediated adiponectin in WT mice resulted in decreased LV dilatation and improved LV function that was associated with increased capillary density in the infarct border zone and decreased myocyte hypertrophy, diminished myocardial apoptosis and decreased interstitial fibrosis in the remote zone. These data suggest that adiponectin protects against the development of systolic dysfunction after myocardial infarction through its abilities to suppress cardiac hypertrophy and interstitial fibrosis, and protect against myocyte and capillary loss.
KW - Heart failure
KW - Ischemia
KW - Myocytes
KW - Ventricular function
UR - http://www.scopus.com/inward/record.url?scp=34249670301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249670301&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2007.03.808
DO - 10.1016/j.yjmcc.2007.03.808
M3 - Article
C2 - 17499764
AN - SCOPUS:34249670301
SN - 0022-2828
VL - 42
SP - 1065
EP - 1074
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 6
ER -