Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells
Published Date:Sep 22 2016
Pubmed Central ID:PMC5097675
Funding:R01 HL080105/HL/NHLBI NIH HHS/United States
R01 OH010828/OH/NIOSH CDC HHS/United States
R01 ES014639/ES/NIEHS NIH HHS/United States
R01 HL128970/HL/NHLBI NIH HHS/United States
K12 GM088021/GM/NIGMS NIH HHS/United States
Description: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.
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.
Supporting Files:No Additional Files
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