Adiponectin protects against the development of systolic dysfunction following myocardial infarction.
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 beta-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.
Shibata
Rei
R
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA.
Izumiya
Yasuhiro
Y
Sato
Kaori
K
Papanicolaou
Kyriakos
K
Kihara
Shinji
S
Colucci
Wilson S
WS
Sam
Flora
F
Ouchi
Noriyuki
N
Walsh
Kenneth
K
D000256:Adenoviridae / Q000235:genetics; D052242:Adiponectin / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure / Q000235:genetics; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000235:genetics; D020257:Ventricular Remodeling / Q000502:physiology*
D052242:Adiponectin; D002316:Cardiotonic Agents