Morimoto Satoshi, Ando Takashi, Niiyama Michita, Seki Yasufumi, Yoshida Naohiro, Watanabe Daisuke, Kawakami-Mori Fumiko, Kobori Hiroyuki, Nishiyama Akira, Ichihara Atsuhiro
Department of Medicine II, Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan.
Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Hypertens Res. 2014 Jul;37(7):642-8. doi: 10.1038/hr.2014.46. Epub 2014 Mar 20.
The (pro)renin receptor ((P)RR) is expressed in several tissues including kidney, heart and brain, and is thought to regulate the tissue renin-angiotensin system (RAS) through the non-proteolytic activation of prorenin. (P)RR is cleaved by furin to generate soluble (P)RR (s(P)RR), which is secreted into the extracellular space. s(P)RR is a candidate biomarker reflecting the status of the tissue RAS. Here, we investigated the relationship between background factors and serum s(P)RR levels. We measured s(P)RR levels in 122 patients with essential hypertension (EH) and assessed the relationships between background factors and s(P)RR levels. Serum s(P)RR levels were 19.0±4.9 ng ml(-1). Single regression analyses showed that age (r=0.251, P<0.01), serum creatinine levels (r=0.229, P<0.05) and urinary angiotensinogen excretion (r=0.196, P<0.05) were positively correlated with s(P)RR levels, whereas estimated glomerular filtration rate (eGFR; r=-0.337, P<0.001) were negatively correlated. Multiple regression analyses of age, blood pressure (BP), hemoglobin A1c (HbA1c) and s(P)RR levels revealed that age and s(P)RR levels were negatively correlated with the eGFR (P<0.05). In patients with EH, serum s(P)RR levels correlated positively with renal function independent of age, BP and HbA1c. These findings support s(P)RR as a useful biomarker that reflects the status of the tissue RAS.
(前)肾素受体((P)RR)在包括肾脏、心脏和大脑在内的多种组织中表达,被认为可通过非蛋白水解激活肾素原来调节组织肾素-血管紧张素系统(RAS)。(P)RR被弗林蛋白酶切割产生可溶性(P)RR(s(P)RR),后者分泌到细胞外空间。s(P)RR是反映组织RAS状态的候选生物标志物。在此,我们研究了背景因素与血清s(P)RR水平之间的关系。我们测量了122例原发性高血压(EH)患者的s(P)RR水平,并评估了背景因素与s(P)RR水平之间的关系。血清s(P)RR水平为19.0±4.9 ng ml⁻¹。单因素回归分析显示,年龄(r = 0.251,P < 0.01)、血清肌酐水平(r = 0.229,P < 0.05)和尿血管紧张素原排泄量(r = 0.196,P < 0.05)与s(P)RR水平呈正相关,而估算肾小球滤过率(eGFR;r = -0.337,P < 0.001)与s(P)RR水平呈负相关。对年龄、血压(BP)、糖化血红蛋白(HbA1c)和s(P)RR水平进行多因素回归分析发现,年龄和s(P)RR水平与eGFR呈负相关(P < 0.05)。在EH患者中,血清s(P)RR水平与肾功能呈正相关,且不受年龄、BP和HbA1c的影响。这些发现支持s(P)RR作为反映组织RAS状态的有用生物标志物。