Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats
Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats
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DOI：
10.1016/j.jjcc.2020.12.009
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发表时间：
2021-05-28
影响因子：
2.5
通讯作者：
Ito, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakamura, Kazufumi;Akagi, Satoshi;Ito, Hiroshi
背景：晚期糖基化终产物受体(RAGE)是一种属于免疫球蛋白超家族的跨膜受体，在肺动脉高压(PAH)患者的肺动脉平滑肌细胞(PASMC)中高表达，参与了PAH的发病机制。最近，我们报道了针对RAGE的一种短链单链DNA RAGE-APTAMER能抑制PAH中培养的PASMC的不适当增加。方法和结果：将大鼠分为空白对照组、野百合碱注射后立即皮下持续给药组和野百合碱注射后立即皮下注射对照适配子组。注射野百合碱和对照适配子或RAGE适配子后，所有大鼠均存活21d。在持续皮下注射对照适配子的同时注射野百合碱，与对照组相比，右室收缩压升高。这种增加可通过持续皮下注射RAGE-适配子而减弱。野百合碱和对照适配子组小动脉完全肌化的比例高于对照组。结论：连续皮下给药抑制野百合碱诱导的大鼠肺动脉高压的形成。抑制RAGE可改善小肺动脉的肌化。使用RAGE-适配子治疗PAH可能是一种新的治疗选择。(C)2020日本心脏病学会。爱思唯尔有限公司出版。保留所有权利。
Background: The receptor for advanced glycation end products (RAGE), a transmembrane receptor be-longing to the immunoglobulin superfamily, is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with pulmonary arterial hypertension (PAH) and is implicated in the etiology of PAH. Recently, we reported that RAGE-aptamer, a short and single-stranded DNA directed against RAGE, inhibited an inappropriate increase in cultured PASMCs in PAH. The aim of this study was to determine the efficacy of RAGE-aptamer in monocrotaline-induced PAH in rats.Methods and Results: Rats were assigned to either an untreated control group, a group that received continuous subcutaneous administration of RAGE-aptamer immediately after monocrotaline injection, or a group that received control-aptamer immediately after monocrotaline injection. All rats survived 21 days after injection of monocrotaline and control-aptamer or RAGE-aptamer. Injection of monocrotaline with continuous subcutaneous delivery of control-aptamer resulted in higher right ventricular systolic pressure compared with controls. This increase was attenuated by continuous subcutaneous delivery of RAGE-aptamer. The proportion of small pulmonary arteries with full muscularization was greater in the monocrotaline and control-aptamer group than in the control group. Continuous subcutaneous delivery of RAGE-aptamer significantly reduced the percentage of small pulmonary arteries with full muscularization.Conclusions: Continuous subcutaneous delivery of RAGE-aptamer suppresses development of monocrotaline-induced PAH in rats. Inhibition of RAGE ameliorates muscularization of small pulmonary arteries. Treatment with RAGE-aptamer might be a new therapeutic option for PAH.(c) 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.