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

Abstract

(Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H+-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and urine. Elevated plasma s(P)RR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(P)RR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS). Interestingly, the levels are elevated in parallel with the severity of OSAS, but are not related to the presence of hypertension or the status of the circulating RAS in OSAS. It is known that v-ATPase activity protects cells from endogenous oxidative stress, and loss of v-ATPase activity results in chronic oxidative stress. We hypothesize that hypoxia and subsequent oxidative stress, perhaps in the brain, may be one of the factors that elevate plasma s(P)RR levels in OSAS.

The Soluble (Pro)Renin Receptor in Health and Diseases: Foe or Friend?

“…These results are consistent with the observations that plasma sPRR concentrations are independent of plasma prorenin/renin and aldosterone levels (Nguyen G et al, 2014). OSAS is characterized by intermittent hypoxia, resulting in oxidative stress in the multiple organs, contributing to the elevation of plasma sPRR levels in patients with OSAS (Takahashi K et al, 2017). In support of this possibility, hypoxia has been reported to significantly increase intracellular sPRR levels in human placental trophoblast cells (Suda C et al, 2020).…”

Edaravone Improves Intermittent Hypoxia-Induced Cognitive Impairment and Hippocampal Damage in Rats

“…OSAHS is an oxidative stress disease, which indicates the role of intermittent hypoxia-induced oxidative stress in the pathogenesis of OSAHS. 17,18) We found that intermittent hypoxia significantly increased the ROS levels in the hippocampus, significantly decreased Mn-SOD and CTA expression, and did not affect Cu/Zn-SOD expression levels. Mn-SOD is expressed in the mitochondria; therefore, oxidative stress may predominantly occur in the mitochondria.…”

Soluble (pro)renin receptor treats metabolic syndrome in mice with diet-induced obesity via interaction with PPARγ

“…Third, circulating sPRR was reduced by 80% and adipose PRR protein expression was suppressed by adipocyte-specific deletion of PPARγ (FKO), but supplementation of sPRR in null mice significantly improved glycemic control. A better understanding of the adipose origin of circulating sPRR is clinically relevant, because elevated plasma sPRR is associated with early pregnancy (11,12), preeclampsia (39,40), gestational diabetes mellitus (12,14), renal dysfunction in patients with heart failure (13), obstructive sleep apnea syndrome (15,41,42), and CKD due to hypertension and type 2 diabetes (43).…”