TY - JOUR
T1 - A pilot study linking endothelial injury in lungs and kidneys in chronic obstructive pulmonary disease
AU - Polverino, Francesca
AU - Laucho-Contreras, Maria E.
AU - Petersen, Hans
AU - Bijol, Vanesa
AU - Sholl, Lynette M.
AU - Choi, Mary E.
AU - Divo, Miguel
AU - Pinto-Plata, Victor
AU - Chetta, Alfredo
AU - Tesfaigzi, Yohannes
AU - Celli, Bartolomé R.
AU - Owen, Caroline A.
N1 - Funding Information:
Supported by Public Health Service, NHLBI (HL063137, HL086814, HL111835, PO1 HL105339, P01 HL114501, HL060234, DK057661, and AI111475-01), Flight Attendants Medical Research Institute (#CIA123046 and YFEL141004), Parker B. Francis Foundation Fellowship, the Brigham and Women's Hospital-Lovelace Respiratory Research Institute Consortium, and the Department of Defense (#PR152060). This study used biologic specimens and data provided by the Lung Tissue Research Consortium supported by the NHLBI.
Publisher Copyright:
© 2017 by the American Thoracic Society.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Rationale: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia. Objectives: 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. Methods: 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, andmeasured 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. Measurements and Main Results: 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. Conclusions: 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 andlung functionby reducing endothelial injury.
AB - Rationale: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia. Objectives: 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. Methods: 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, andmeasured 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. Measurements and Main Results: 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. Conclusions: 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 andlung functionby reducing endothelial injury.
KW - COPD
KW - Cigarette smoke
KW - Comorbidities
KW - Endothelium
KW - Kidney
UR - http://www.scopus.com/inward/record.url?scp=85020181496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020181496&partnerID=8YFLogxK
U2 - 10.1164/rccm.201609-1765OC
DO - 10.1164/rccm.201609-1765OC
M3 - Article
C2 - 28085500
AN - SCOPUS:85020181496
SN - 1073-449X
VL - 195
SP - 1464
EP - 1476
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 11
ER -