TY - JOUR
T1 - Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells
AU - Zychowski, Katherine E.
AU - Sanchez, Bethany
AU - Pedrosa, Rodrigo P.
AU - Lorenzi-Filho, Geraldo
AU - Drager, Luciano F.
AU - Polotsky, Vsevolod Y.
AU - Campen, Matthew J.
N1 - Funding Information:
This research was sponsored by NIGMS ( K12GM088021 ), NIEHS ( ES014639 ), NIOSH ( OH010828 ), and NHLBI ( HL128970 and HL080105 ).
Publisher Copyright:
© 2016 Elsevier Ireland Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Background and aims 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. Methods 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. Results 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. Conclusions OSA results in greater serum inflammatory potential, thereby driving endothelial activation and dysfunction.
AB - Background and aims 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. Methods 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. Results 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. Conclusions OSA results in greater serum inflammatory potential, thereby driving endothelial activation and dysfunction.
KW - Bioassay
KW - Hypoxia
KW - Inflammation
KW - Obstructive sleep apnea
KW - Serum
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U2 - 10.1016/j.atherosclerosis.2016.09.017
DO - 10.1016/j.atherosclerosis.2016.09.017
M3 - Article
C2 - 27693879
AN - SCOPUS:84988967952
SN - 0021-9150
VL - 254
SP - 59
EP - 66
JO - Atherosclerosis
JF - Atherosclerosis
ER -