中枢神经系统肾素（原）受体参与高血压发病机制的研究进展

doi:10.3969/j.issn.1673-5765.2019.12.015

摘要/Abstract

摘要：

肾素（原）受体是由ATP6AP2基因编码、350个氨基酸组成的Ⅰ型单次跨膜蛋白，广泛存在于多种组织器官中，并在大脑中高度表达。中枢神经系统肾素（原）受体与高血压密切相关，并通过促进血管紧张素Ⅱ形成的肾素-血管紧张素系统机制以及其他非肾素-血管紧张素系统机制参与血压调节。中枢神经系统肾素（原）受体有可能成为高血压治疗新靶点。

文章导读： 中枢神经系统PRR通过RAS及非RAS机制参与血压的调节，其相关机制研究有利于开发新型PRR拮抗剂，并有可能成为高血压治疗的新靶点。

关键词: 中枢神经系统; 肾素（原）受体; 高血压

Abstract:

The (pro) renin receptor is a type I single transmembrane protein composed of 350 amino acids and encoded by the ATP6AP2 gene. It is widely distributed in various tissues and organs and is highly expressed in the brain. The central nervous system (pro) renin receptor is closely related to hypertension, and are involved in blood pressure regulation through reninangiotensin system (RAS) dependent signaling pathway and other signaling pathways. The central nervous system (pro) renin receptor may become a new target for hypertension treatment.

Key words: Central nervous system; (Pro) Renin receptor; Hypertension

唐欣颖, 匡泽民, 卢玺峰. 中枢神经系统肾素（原）受体参与高血压发病机制的研究进展[J]. 中国卒中杂志, 2019, 14(12): 1279-1282.

TANG Xin-Ying, KUANG Ze-Min, LU Xi-Feng. Progress of Central Nervous System (Pro) Renin Receptor in the Pathogenesis of Hypertension[J]. Chinese Journal of Stroke, 2019, 14(12): 1279-1282.

参考文献

[1] REN L，SUN Y，LU H，et al. （Pro）renin receptor

inhibition reprograms hepatic lipid metabolism

and protects mice from diet-induced obesity and

hepatosteatosis[J]. Circ Res，2018，122（5）：730-741.

[2] NARUMI K，SATO E，HIROSE T，et al. （Pro）

renin receptor is involved in mesangial fibrosis and

matrix expansion[J]. Sci Rep，2018，8（1）：16.

[3] KANDA A，ISHIDA S. （Pro）renin receptor：

involvement in diabetic retinopathy and development

of molecular targeted therapy[J]. J Diabetes Investig，

2019，10（1）：6-17.

[4] YU S，YUAN H，YANG M，et al. （Pro）renin

receptor RNA interference silencing attenuates

diabetic cardiomyopathy pathological process in

rats[J]. Hum Gene Ther，2019，30（6）：727-739.

[5] BRACKE A，VON BOHLEN UND HALBACH

O. Roles and functions of Atp6ap2 in the brain[J].

Neural Regen Res，2018，13（12）：2038-2043.

[6] HENNRIKUS M，GONZALEZ A A，PRIETO M C.

The prorenin receptor in the cardiovascular system

and beyond[J]. Am J Physiol Heart Circ Physiol，

2018，314（2）：H139-H145.

[7] PETERS J. The（pro）renin receptor and its

interaction partners[J]. Pflugers Arch，2017，469

（10）：1245-1256.

[8] XU Q，JENSEN D D，PENG H，et al. The critical

role of the central nervous system（pro）renin

receptor in regulating systemic blood pressure[J/OL].

Pharmacol Ther，2016，164：126-134. https：//doi.

org/10.1016/j.pharmthera.2016.04.006.

[9] LABANDEIRA-GARCÍA J L，GARRIDO-GIL P，

Rodriguez-Pallares J，et al. Brain renin-angiotensin

system and dopaminergic cell vulnerability[J/

OL]. Front Neuroanat，2014，8：67. https：//doi.

org/10.3389/fnana.2014.00067.

[10] AMES M K，ATKINS C E，PITT B. The reninangiotensin-

aldosterone system and its suppression[J].

J Vet Intern Med，2019，33（2）：363-382.

[11] NGUYEN G，BURCKLÉ C A，SRAER J D. Renin/

prorenin-receptor biochemistry and functional

significance[J]. Curr Hypertens Rep，2004，6（2）：

129-132.

[12] LI W，PENG H，MEHAFFEY E P，et al. Neuronspecific（

pro）renin receptor knockout prevents

the development of salt-sensitive hypertension[J].

Hypertension，2014，63（2）：316-323.

[13] COOPER S G，TRIVEDI D P，YAMAMOTO R，et

al. Increased（pro）renin receptor expression in

the subfornical organ of hypertensive humans[J].

Am J Physiol Heart Circ Physiol，2018，314（4）：

H796-H804.

[14] VAN THIEL B S，GÓES MARTINI A，TE RIET

L，et al. Brain renin-angiotensin system：does it

exist?[J]. Hypertension，2017，69（6）：1136-1144.

[15] SUN Y，DANSER A，LU X. （Pro）renin

receptor as a therapeutic target for the treatment

of cardiovascular diseases?[J/OL]. Pharmacol Res，

2017，125（Pt A）：48-56. https：//doi.org/10.1016/

j.phrs.2017.05.016.

[16] TREPICCIONE F，GERBER S D，GRAHAMMER F，

et al. Renal Atp6ap2/（pro）renin receptor is required

for normal vacuolar H+-ATPase function but not for

the renin-angiotensin system[J]. J Am Soc Nephrol，

2016，27（11）：3320-3330.

[17] LI W，SULLIVAN M N，ZHANG S，et al. Intracerebro-

ventricular infusion of the（pro）renin receptor

antagonist PRO20 attenuates deoxycorticosterone

acetate-salt-induced hypertension[J]. Hypertension，

2015，65（2）：352-361.

[18] DANSER A H. The role of the（pro）renin receptor

in hypertensive disease[J]. Am J Hypertens，2015，28

（10）：1187-1196.

[19] HUBER M J，BASU R，CECCHETTINI C，et

al. Activation of the（pro）renin receptor in the

paraventricular nucleus increases sympathetic

outflow in anesthetized rats[J]. Am J Physiol Heart

Circ Physiol，2015，309（5）：H880-H887.

[20] PITRA S，FENG Y，STERN J E. Mechanisms

underlying prorenin actions on hypothalamic

neurons implicated in cardiometabolic control[J].

Mol Metab，2016，5（10）：858-868.

[21] PENG H，JENSEN D D，LI W，et al. Overexpression

of the neuronal human（pro）renin receptor mediates

angiotensin Ⅱ-independent blood pressure regulation

in the central nervous system[J]. Am J Physiol Heart

Circ Physiol，2018，314（3）：H580-H592.

[22] RAMKUMAR N，KOHAN D E. The（pro）renin

receptor：an emerging player in hypertension and

metabolic syndrome[J]. Kidney Int，2019，95（5）：

1041-1052.

[23] DUBOS A，CASTELLS-NOBAU A，MEZIANE H，

et al. Conditional depletion of intellectual disability

and Parkinsonism candidate gene ATP6AP2 in

fly and mouse induces cognitive impairment and

neurodegeneration[J]. Hum Mol Genet，2015，24

（23）：6736-6755.