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

Abstract

(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.

Water Deprivation Increases (Pro)renin Receptor Levels in the Kidney and Decreases Plasma Concentrations of Soluble (Pro)renin Receptor

“…Nguyen et al (2014) reported that plasma levels of s(P)RR were independent of plasma renin, prorenin, and aldosterone concentrations in man. Moreover, plasma levels of s(P)RR showed no significant correlation with PRA or plasma aldosterone levels in patients with obstructive sleep apnea syndrome (Nishijima et al 2014(Nishijima et al , 2016. It has been reported that most soluble receptors act as antagonists and compete with their membrane-associated counterparts for ligands (RoseJohn et al 2006;Tracey et al 2008).…”

“…Plasma concentrations of s(P)RR were elevated in patients with chronic kidney disease (Hamada et al 2013), pregnant women with the development of gestational diabetes mellitus or hypertension later in pregnancy (Watanabe et al 2012(Watanabe et al , 2013, and patients with obstructive sleep apnea syndrome (Nishijima et al 2014(Nishijima et al , 2016.…”

Expression of (Pro)renin Receptor During Rapamycin-Induced Erythropoiesis in K562 Erythroleukemia Cells and Its Possible Dual Actions on Erythropoiesis

“…Previous studies have suggested that (P)RR is related to the pathophysiology of various diseases, such as hypertension, diabetes mellitus, kidney disease (Ichihara et al 2004(Ichihara et al , 2006, dehydration (Tamura et al 2016), and obstructive sleep apnea syndrome (Nishijima et al 2016). The present study has shown that expression levels of (P)RR are elevated during rapamycin-induced erythropoiesis, and (P) RR may have dual actions on erythropoiesis in K562 erythroleukemic cells; the promotion of erythropoiesis via the functional complex formation with v-ATPase, and the negative regulation on ALAS2 mRNA expression.…”

Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

“…In contrast, Svatikova et al [48] showed no significant changes in plasma aldosterone levels in OSAS patients. Because OSAS patients were frequently accompanied by hypertension and diabetes mellitus, we studied plasma concentrations of s(P)RR in OSAS patients [22,23]. …”

“…We have recently reported that plasma concentrations of s(P)RR are elevated in patients with obstructive sleep apnea syndrome (OSAS) in parallel with the severity of disease [22,23]. In this review article, we review plasma concentrations of s(P)RR in patients with various diseases including OSAS, and discuss the possible relation between plasma s(P)RR and oxidative stress.…”