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Adiponectin Deficiency Increases Allergic Airway Inflammation and Pulmonary Vascular Remodeling

¹ Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, ² Pulmonary and Critical Care Unit, and ⁴ Cardiovascular Research Center and Anesthesia Center for Critical Care Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts; ³ Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; and ⁵ Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

Correspondence and requests for reprints should be addressed to Benjamin D. Medoff, M.D., Massachusetts General Hospital, CNY 8301, 149 13th Street, Charlestown, MA 02129. E-mail: bmedoff{at}partners.org or aluster{at}mgh.harvard.edu

Obesity is associated with an increased incidence and severity of asthma, as well as other lung disorders, such as pulmonary hypertension. Adiponectin (APN), an antiinflammatory adipocytokine, circulates at lower levels in the obese, which is thought to contribute to obesity-related inflammatory diseases. We sought to determine the effects of APN deficiency in a murine model of chronic asthma. Allergic airway inflammation was induced in APN-deficient mice (APN^–/–) using sensitization without adjuvant followed by airway challenge with ovalbumin. The mice were then analyzed for changes in inflammation and lung remodeling. APN^–/– mice in this model develop increased allergic airway inflammation compared with wild-type mice, with greater accumulation of eosinophils and monocytes in the airways associated with elevated lung chemokine levels. Surprisingly, APN^–/– mice developed severe pulmonary arterial muscularization and pulmonary arterial hypertension in this model, whereas wild-type mice had only mild vascular remodeling and comparatively less pulmonary arterial hypertension. Our findings demonstrate that APN modulates allergic inflammation and pulmonary vascular remodeling in a model of chronic asthma. These data provide a possible mechanism for the association between obesity and asthma, and suggest a potential novel link between obesity, inflammatory lung disease, and pulmonary hypertension.

Key Words: asthma • obesity • pulmonary hypertension

CLINICAL RELEVANCE The research presented in this article provides a mechanism that might explain the increased incidence of asthma in the obese. Furthermore, the data suggest a novel mechanism by which obesity may influence the development of pulmonary hypertension in the presence of inflammatory lung disease.

 

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