Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease.
Adiponectin (APN) is an adipocyte-derived factor that exists at high concentrations in serum and has anti-inflammatory and systemic vascular-protective properties. In this study, we investigated the role of APN in pulmonary vascular homeostasis. We found that APN localizes to the luminal side of blood vessels in lung and acts in vitro to block TNF-alpha-induced E-selectin upregulation in pulmonary artery endothelial cells. Targeted deletion of the APN gene in mice leads to a vascular phenotype in lung characterized by E-selectin upregulation and age-dependent increases in perivascular inflammatory cell infiltration and pulmonary arterial pressures. Taken together, these findings demonstrate an important role for APN in lung vascular homeostasis and suggest that APN-deficient states may contribute to the pathogenesis of inflammatory pulmonary vascular disease and to the development of pulmonary hypertension.
Summer
Ross
R
The Pulmonary Center, R-304, Boston Univ. School of Medicine, 80 East Concord St., Boston, MA 02118, USA. rsummer@bu.edu
Fiack
Christopher A
CA
Ikeda
Yasumasa
Y
Sato
Kaori
K
Dwyer
Daniel
D
Ouchi
Noriyuki
N
Fine
Alan
A
Farber
Harrison W
HW
Walsh
Kenneth
K
D052242:Adiponectin / Q000172:deficiency* / Q000378:metabolism*; D000375:Aging / Q000473:pathology; D000818:Animals; D006328:Cardiac Catheterization; D002460:Cell Line; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D010641:Phenotype; D011312:Pressure; D021381:Protein Transport / Q000187:drug effects; D011651:Pulmonary Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014463:Ultrasonography; D015854:Up-Regulation / Q000187:drug effects; D014652:Vascular Diseases / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology
D052242:Adiponectin; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha