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Evaluation of endothelial dysfunction in the pharyngeal wall in patients with Obstructive Sleep Apnea

Grant number: 20/09089-8
Support Opportunities:Regular Research Grants
Duration: December 01, 2020 - November 30, 2023
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Michel Burihan Cahali
Grantee:Michel Burihan Cahali
Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated researchers:Luiz Ubirajara Sennes ; Thais Mauad


Obstructive sleep apnea (OSA) is a prevalent sleep disordered breathing associated with long-term cardiovascular morbidity. The pathophysiology of the cardiovascular morbidities in OSA involves endothelial dysfunction, increased sympathetic activation, arterial stiffening and chronic systemic inflammation. Endothelial dysfunction is often considered one of the earliest detectable and possibly reversible abnormalities during the development of atherosclerosis. The possible sources of endothelial dysfunction in OSA include repetitive hypoxemia with reactive oxygen species generation and systemic inflammation. The serum levels of some inflammatory markers seem increased in patients with OSA. The pharynx is the primary organ involved in OSA, suffering from chronic vibration due to snoring and also from recurrent episodes of narrowing and collapses associated with increased inspiratory pressure during the obstructive events of OSA. The involvement of the lateral pharyngeal walls in OSA has been already demonstrated. The presence of markers of endothelial dysfunction in the vessels of the lateral pharyngeal muscular wall has not been investigated and represents a potential ultra early marker of endothelial dysfunction onset in OSA. The purpose of this study is to quantify important inflammatory markers in the vessels of the pharyngeal muscles in OSA subjects, primary snorers and non-OSA non-snorer controls in order to verify how early this source of endothelial injury may occur according to the severity of OSA. Methods: We will evaluate biopsies of the deep pharyngeal muscular wall (superior constrictor pharyngeal muscle) that were obtained during pharyngeal surgeries in OSA patients (28 cases), primary snorers (18 cases) and non-OSA non-snorer subjects (14 cases). These surgeries were performed in the years 2005 and 2006 and those specimens were conserved in paraffin blocks. Sections of these blocks were used in a previous histological study from our group. The specimens will be stained with the following biological markers of endothelial dysfunction: ENDOCAN (ESM-1), vascular endothelial growth factor (VEGF), vascular cell adhesion molecule (VCAM-1), Endothelin-1(ET-1) and E-selectin (E-SELECTIN) expression. Each of those markers will be quantified in the vessels of every specimen and the studied groups will be compared according to the expression of each one of those markers. (AU)

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