Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin.
Adiponectin is an adipocyte-derived, antiatherogenic protein that is present in serum as three isoforms. Total adiponectin levels are decreased in obese or diabetic humans or animal models. This study was designed to elucidate the relative isoform distribution of adiponectin in human disease states and identify the active form of adiponectin toward vascular endothelial cells. The percentage of high molecular weight form (HMW) per total adiponectin was significantly lower in patients with coronary artery disease than control subjects, whereas the hexamer form was similar and the trimer form was significantly higher. During weight reduction in obese subjects, the HMW form increased and the trimer and hexamer forms decreased. Recombinant adiponectin dose-dependently suppressed apoptosis and caspase-3 activity in human umbilical vein endothelial cells (HUVECs). Transduction with dominant-negative AMP-activated protein kinase (AMPK) abolished the suppressive effect of adiponectin on HUVECs. Gel filtration chromatography was used to separate the adiponectin isoforms, and the antiapoptotic effect toward HUVECs was only observed with the HMW form. These data suggest that HMW adiponectin specifically confers the vascular-protective activities of this adipocytokine. The full text of this article is available online at http://circres.ahajournals.org.
Kobayashi
Hideki
H
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Ouchi
Noriyuki
N
Kihara
Shinji
S
Walsh
Kenneth
K
Kumada
Masahiro
M
Abe
Yuki
Y
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
D055372:AMP-Activated Protein Kinases; D052242:Adiponectin; D017209:Apoptosis / Q000187:drug effects*; D001704:Biopolymers; D002318:Cardiovascular Diseases / Q000209:etiology; D003327:Coronary Disease / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000235:genetics / Q000502:physiology; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000178:diet therapy; D020033:Protein Isoforms / Q000097:blood / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015431:Weight Loss
D052242:Adiponectin; D001704:Biopolymers; D036341:Intercellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases