title: Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.
abstract: Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Dilip
authors.initials: D
authors.lastname: Shah
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Freddy
authors.initials: F
authors.lastname: Romero
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Duong
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Nadan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Bishnuhari
authors.initials: B
authors.lastname: Paudyal
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Suratt
authors.affiliation: Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Caleb B
authors.initials: CB
authors.lastname: Kallen
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Sun
authors.affiliation: 1] Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA [2] Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, 02118, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.affiliation: Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Summer
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000209:etiology / Q000473:pathology; D054392:Adipokines / Q000097:blood*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008806:Mice, Inbred AKR; D008811:Mice, Inbred DBA; D009765:Obesity / Q000097:blood / Q000150:complications / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology / Q000473:pathology
chemical_list: D054392:Adipokines; D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides