Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity

Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity

TSUGUO NISHIJIMA,¹ KAZUKI TAJIMA,² YOSHIHIRO YAMASHIRO,¹ KEISUKE HOSOKAWA,¹ AKIRA SUWABE,³ KAZUHIRO TAKAHASHI² and SHIGERU SAKURAI¹

¹Division of Behavioral Sleep Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan
²Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
³Department of Laboratory Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan

(Pro)renin receptor ((P)RR), a receptor for renin and prorenin, is implicated in the pathophysiology of diabetes mellitus, hypertension and their complications. Soluble (P)RR (s(P)RR) is composed of extracellular domain of (P)RR and thus exists in blood. We have reported that plasma concentrations of s(P)RR were elevated in male patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study was to clarify the difference in plasma s(P)RR concentrations between male and female OSAS patients. Plasma s(P)RR concentrations were studied in 289 subjects (206 males and 83 females) consisting of 259 OSAS patients and 30 non-OSAS control subjects. The 259 OSAS patients were classified into mild (5 ≤ apnea hypopnea index (AHI) < 15 events/h), moderate (15 ≤ AHI < 30), and severe OSAS (AHI ≥ 30). Plasma s(P)RR levels were significantly elevated in all three OSAS groups compared to non-OSAS control subjects (AHI < 5) in the entire cohort and male subjects, whereas in female subjects, the significant elevation was found only in severe OSAS. Plasma s(P)RR levels were significantly correlated with AHI in both sexes, with a higher r value found in male subjects (male r = 0.413, p < 0.0001; female r = 0.263, p < 0.05). Importantly, when OSAS patients (26 males and 15 females) with AHI ≥ 20 underwent continuous positive airway pressure treatment, plasma s(P)RR levels were significantly decreased. In conclusion, plasma s(P)RR levels are elevated in both male and female OSAS patients in parallel with the disease severity.

keywords —— apnea hypopnea index; arousal index; obstructive sleep apnea syndrome; sex differences; soluble (pro)renin receptor

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Tohoku J. Exp. Med., 2016, 238, 325-338

Correspondence: Tsuguo Nishijima, M.D., Ph.D., Division of Behavioral Sleep Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan.

e-mail: tsuguo@ck9.so-net.ne.jp or tsuguo@iwate-med.ac.jp