title: A Pilot Study Linking Endothelial Injury in Lungs and Kidneys in Chronic Obstructive Pulmonary Disease.
abstract: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia.
  
  
  
  To determine whether (1) cigarette smoke (CS)-induced pulmonary and renal endothelial cell injury explains the association between albuminuria and COPD, (2) CS-induced albuminuria is linked to increases in the oxidative stress-advanced glycation end products (AGEs) receptor for AGEs (RAGE) pathway, and (3) enalapril (which has antioxidant properties) limits the progression of pulmonary and renal injury by reducing activation of the AGEs-RAGE pathway in endothelial cells in both organs.
  
  
  
  In 26 patients with COPD, 24 ever-smokers without COPD, 32 nonsmokers who underwent a renal biopsy or nephrectomy, and in CS-exposed mice, we assessed pathologic and ultrastructural renal lesions, and measured urinary albumin/creatinine ratios, tissue oxidative stress levels, and AGEs and RAGE levels in pulmonary and renal endothelial cells. The efficacy of enalapril on pulmonary and renal lesions was assessed in CS-exposed mice.
  
  
  
  Patients with COPD and/or CS-exposed mice had chronic renal injury, increased urinary albumin/creatinine ratios, and increased tissue oxidative stress and AGEs-RAGE levels in pulmonary and renal endothelial cells. Treating mice with enalapril attenuated CS-induced increases in urinary albumin/creatinine ratios, tissue oxidative stress levels, endothelial cell AGEs and RAGE levels, pulmonary and renal cell apoptosis, and the progression of chronic renal and pulmonary lesions.
  
  
  
  Patients with COPD and/or CS-exposed mice have pulmonary and renal endothelial cell injury linked to increased endothelial cell AGEs and RAGE levels. Albuminuria could identify patients with COPD in whom angiotensin-converting enzyme inhibitor therapy improves renal and lung function by reducing endothelial injury.
authors.affiliation: 1 Pulmonary Division and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.|3 University of Parma, Parma, Italy.
authors.forename: Francesca
authors.identifier: 0000-0001-9686-5698
authors.initials: F
authors.lastname: Polverino
authors.affiliation: 4 Universidad Central de Venezuela, Caracas, Venezuela; and.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Laucho-Contreras
authors.affiliation: 2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Hans
authors.initials: H
authors.lastname: Petersen
authors.affiliation: 5 Pathology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bijol
authors.affiliation: 5 Pathology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
authors.affiliation: 6 Nephrology Division, Weill Cornell Medical College, New York, New York.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Choi
authors.affiliation: 1 Pulmonary Division and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Divo
authors.affiliation: 1 Pulmonary Division and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Victor
authors.initials: V
authors.lastname: Pinto-Plata
authors.affiliation: 3 University of Parma, Parma, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Chetta
authors.affiliation: 2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.affiliation: 1 Pulmonary Division and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Bartolomé R
authors.initials: BR
authors.lastname: Celli
authors.affiliation: 1 Pulmonary Division and.|2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Caroline A
authors.identifier: 0000-0003-4377-3591
authors.initials: CA
authors.lastname: Owen
mesh_terms: D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018384:Oxidative Stress; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*
keywords: COPD; cigarette smoke; comorbidities; endothelium; kidney