Selective Suppression of Endothelial Cell Apoptosis by the High Molecular Weight Form of Adiponectin
ABSTRACT—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 diseas...
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| Published in | Circulation research Vol. 94; no. 4; pp. e27 - e31 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Heart Association, Inc
05.03.2004
Lippincott Williams & Wilkins Ovid Technologies |
| Subjects | |
| Online Access | Get full text |
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| Abstract | ABSTRACT—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. |
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| AbstractList | 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. ABSTRACT—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. 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 . 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.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. 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. |
| Author | Matsuzawa, Yuji Kumada, Masahiro Walsh, Kenneth Funahashi, Tohru Kobayashi, Hideki Kihara, Shinji Ouchi, Noriyuki Abe, Yuki |
| AuthorAffiliation | From the Department of Internal Medicine and Molecular Science (H.K., S.K., M.K., T.F., Y.M.), Graduate School of Medicine, Osaka University, Osaka, Japan; Molecular Cardiology/Whitaker Cardiovascular Institute (N.O., K.W.), Boston University School of Medicine, Boston, Mass; Lead Discovery Research Laboratories (Y.A.), Sankyo Co Ltd, Tokyo, Japan |
| AuthorAffiliation_xml | – name: From the Department of Internal Medicine and Molecular Science (H.K., S.K., M.K., T.F., Y.M.), Graduate School of Medicine, Osaka University, Osaka, Japan; Molecular Cardiology/Whitaker Cardiovascular Institute (N.O., K.W.), Boston University School of Medicine, Boston, Mass; Lead Discovery Research Laboratories (Y.A.), Sankyo Co Ltd, Tokyo, Japan |
| Author_xml | – sequence: 1 givenname: Hideki surname: Kobayashi fullname: Kobayashi, Hideki organization: From the Department of Internal Medicine and Molecular Science (H.K., S.K., M.K., T.F., Y.M.), Graduate School of Medicine, Osaka University, Osaka, Japan; Molecular Cardiology/Whitaker Cardiovascular Institute (N.O., K.W.), Boston University School of Medicine, Boston, Mass; Lead Discovery Research Laboratories (Y.A.), Sankyo Co Ltd, Tokyo, Japan – sequence: 2 givenname: Noriyuki surname: Ouchi fullname: Ouchi, Noriyuki – sequence: 3 givenname: Shinji surname: Kihara fullname: Kihara, Shinji – sequence: 4 givenname: Kenneth surname: Walsh fullname: Walsh, Kenneth – sequence: 5 givenname: Masahiro surname: Kumada fullname: Kumada, Masahiro – sequence: 6 givenname: Yuki surname: Abe fullname: Abe, Yuki – sequence: 7 givenname: Tohru surname: Funahashi fullname: Funahashi, Tohru – sequence: 8 givenname: Yuji surname: Matsuzawa fullname: Matsuzawa, Yuji |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/14752031$$D View this record in MEDLINE/PubMed |
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| CODEN | CIRUAL |
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| Snippet | ABSTRACT—Adiponectin is an adipocyte-derived, antiatherogenic protein that is present in serum as three isoforms. Total adiponectin levels are decreased in... Adiponectin is an adipocyte-derived, antiatherogenic protein that is present in serum as three isoforms. Total adiponectin levels are decreased in obese or... |
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| SubjectTerms | Adiponectin AMP-Activated Protein Kinases Apoptosis - drug effects Biopolymers Cardiovascular Diseases - etiology Coronary Disease - blood Dose-Response Relationship, Drug Endothelial Cells - drug effects Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Female Humans Intercellular Signaling Peptides and Proteins Male Middle Aged Molecular Weight Multienzyme Complexes - genetics Multienzyme Complexes - physiology Obesity - blood Obesity - complications Obesity - diet therapy Protein Isoforms - blood Protein Isoforms - pharmacology Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - physiology Proteins - analysis Proteins - chemistry Proteins - pharmacology Recombinant Fusion Proteins - physiology Recombinant Proteins - pharmacology Structure-Activity Relationship Weight Loss |
| Title | Selective Suppression of Endothelial Cell Apoptosis by the High Molecular Weight Form of Adiponectin |
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