Essential roles of angiotensin II in vascular endothelial growth factor expression in sleep apnea syndrome.
BACKGROUND
Hypoxia-induced endothelial cell dysfunction has been implicated in increased cardiovascular disease associated with obstructive sleep apnea syndrome (OSAS). OSAS mediates hypertension by stimulating angiotensin II (Ang II) production. Hypoxia and Ang II are the major stimuli of vascular endothelial growth factor (VEGF), which is a potent angiogenic cytokine and also contributes to the atherogenic process itself.


RESULTS
We observed serum Ang II and VEGF levels and peripheral blood mononuclear cell (PBMC) and neutrophil VEGF expression. Compared to controls, subjects with OSAS had significantly increased levels of serum Ang II and VEGF and VEGF mRNA expression in their leukocytes. To examine whether Ang II stimulates VEGF expression in OSAS, we treated PBMCs obtained from control subjects with Ang II and with an Ang II receptor type 1 (AT(1)) blocker, olmesartan. We observed an increased expression of VEGF in the Ang II-stimulated PBMCs and decreased in VEGF mRNA and protein expression in the PBMCs treated with olmesartan.


CONCLUSIONS
These findings suggest that the Ang II-AT(1) receptors pathway potentially are involved in OSAS and VEGF-induced vascularity and that endothelial dysfunction might be linked to this change in Ang II activity within leukocytes of OSAS patients.
Takahashi
Susumu
S
Third Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan.
Nakamura
Yutaka
Y
Nishijima
Tsuguo
T
Sakurai
Shigeru
S
Inoue
Hiroshi
H
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000097:blood / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012891:Sleep Apnea Syndromes / Q000097:blood*; D013777:Tetrazoles / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics
D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; C437965:olmesartan