Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells.
Obstructive sleep apnea (OSA) is characterized by intermittent airway obstruction and systemic hypoxia during sleep, which can contribute to an increase in reactive oxygen species, vascular remodeling, vasoconstriction and ultimately cardiovascular disease. Continuous positive airway pressure (CPAP) is a clinical therapy that maintains airway patency and mitigates several symptoms of OSA. However, it is currently unknown whether CPAP therapy also reduces the overall inflammatory potential in the circulation; to address this in an unbiased manner, we applied a novel endothelial biosensor approach, the serum cumulative inflammatory potential (SCIP) assay.



We studied healthy controls (n = 7), OSA subjects receiving no treatment, (OSA controls) (n = 7) and OSA subjects receiving CPAP for 3 months (n = 8). Serum was obtained from OSA subjects before and after CPAP or no treatment. A battery of quantitative and functional assays was performed to assess the serum inflammatory potential, in terms of endothelial responses. For the SCIP assay, human coronary artery endothelial cells (hCAECs) were incubated with 5% serum in media from individual subjects for 4 h. qPCR was performed to assess endothelial inflammatory transcript (ICAM-1, VCAM-1, IL-8, P-selectin, CCL5, and CXCL12) responses to serum. Additionally, transendothelial resistance was measured in serum-incubated hCAECs following leukocyte challenge.



hCAECs exhibited significant increases in VCAM-1, ICAM-1, IL-8 and P-selectin mRNA when incubated with serum from OSA patients compared to serum from healthy control subjects. Furthermore, compared to no treatment, serum from CPAP-treated individuals was less potent at inducing inflammatory gene expression in the SCIP assay. Similarly, in a leukocyte adhesion assay, naïve cells treated with serum from patients who received CPAP exhibited improved endothelial barrier function than cells treated with OSA control serum.



OSA results in greater serum inflammatory potential, thereby driving endothelial activation and dysfunction.
Department of Pharmaceutical Sciences, University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
Katherine E
KE
Zychowski
Department of Pharmaceutical Sciences, University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
Bethany
B
Sanchez
University of São Paulo Medical School, São Paulo, Brazil; Hospital Metropolitano Sul Dom Helder Câmara - IMIP Hospitalar, Brazil.
Rodrigo P
RP
Pedrosa
University of São Paulo Medical School, São Paulo, Brazil.
Geraldo
G
Lorenzi-Filho
University of São Paulo Medical School, São Paulo, Brazil.
Luciano F
LF
Drager
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Vsevolod Y
VY
Polotsky
Department of Pharmaceutical Sciences, University of New Mexico College of Pharmacy, Albuquerque, NM, USA. Electronic address: mcampen@salud.unm.edu.
Matthew J
MJ
Campen
D000328:Adult; D015374:Biosensing Techniques; D016022:Case-Control Studies; D002448:Cell Adhesion; D015331:Cohort Studies; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D003331:Coronary Vessels / Q000473:pathology*; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000378:metabolism; D007249:Inflammation / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C508606:CXCL8 protein, human; C573420:ICAM1 protein, human; D016209:Interleukin-8; D019007:P-Selectin; C546937:SELP protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
Bioassay; Hypoxia; Inflammation; Obstructive sleep apnea; Serum
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