Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells

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art_ZYCHOWSKI_Serum_from_obstructive_sleep_apnea_patients_induces_inflammatory_2016.PDF (1.07 MB)
Citações na Scopus
48
Tipo de produção
article
Data de publicação
2016
Editora
ELSEVIER IRELAND LTD
DOI
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Scopus
Web of Science
PubMed
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Título do Volume
Autores
ZYCHOWSKI, Katherine E.
SANCHEZ, Bethany
POLOTSKY, Vsevolod Y.
CAMPEN, Matthew J.
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Citação
ATHEROSCLEROSIS, v.254, p.59-66, 2016
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
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, naive 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.
Palavras-chave
Obstructive sleep apnea, Inflammation, Hypoxia, Serum, Bioassay
URI
https://observatorio.fm.usp.br/handle/OPI/17805
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/09
Artigos e Materiais de Revistas Científicas - ODS/03