Pathogenic role of angiotensin II and oxidised LDL in obstructive sleep apnoea.
A sustained elevation of oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) might help to explain their increased risk for cardiovascular diseases. We tested the hypothesis that the values of oxidative stress are increased in otherwise healthy subjects with OSAS when compared with closely matched control subjects. We performed a prospective study of 38 subjects who did not have OSAS and 37 patients with OSAS. Plasma indices of angiotensin (Ang) II, vascular endothelial growth factor (VEGF), oxidised low-density lipoprotein (oxLDL), and circulating endothelial precursor cells (CEPs) were measured in OSAS patients and in matched controls. Peripheral blood mononuclear cells (PBMCs) were obtained from both groups and co-cultured with endothelial cells to examine the effects on tube formation. The OSAS group showed increased levels of Ang II, VEGF, oxLDL and CEPs, which were decreased after nasal continuous positive airway pressure (nCPAP) treatment. In vitro, PBMCs from the OSAS group induced tube formation. Ang II, oxLDL, and Ang II-stimulated PBMCs induced lectin-like oxLDL receptor (LOX-1) expression and VEGF receptor-2 activation on endothelial cells, respectively. These observations suggest an important role of Ang II and oxLDL-mediated LOX-1 upregulation in endothelial cell injury in patients with OSAS.
Kizawa
T
T
Division of Pulmonary Medicine, Allergy, and Rheumatology, Dept of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
Nakamura
Y
Y
Takahashi
S
S
Sakurai
S
S
Yamauchi
K
K
Inoue
H
H
D000328:Adult; D000804:Angiotensin II / Q000378:metabolism* / Q000502:physiology*; D001011:Aorta / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood; D018920:Coculture Techniques; D045422:Continuous Positive Airway Pressure; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D008077:Lipoproteins, LDL; D051127:Scavenger Receptors, Class E; D042461:Vascular Endothelial Growth Factor A; C099252:oxidized low density lipoprotein; D000804:Angiotensin II