The Orphan Receptor GPR35 Contributes to Angiotensin II-Induced Hypertension and Cardiac Dysfunction in Mice.
The Orphan Receptor GPR35 Contributes to Angiotensin II-Induced Hypertension and Cardiac Dysfunction in Mice.
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DOI：
10.1093/ajh/hpy073
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发表时间：
2018-08-03
影响因子：
3.2
通讯作者：
Nicklin SA
中科院分区：
文献类型：
--
作者：
Divorty N;Milligan G;Graham D;Nicklin SA
孤儿受体G蛋白偶联受体35(GPR35)与一系列疾病有关，包括癌症、炎症性肠病、糖尿病、高血压和心力衰竭。为了评估GPR35作为心血管疾病治疗靶点的潜力，本研究调查了GPR35基因敲除小鼠在基础条件和随后的病理生理刺激下的心血管表型。使用植入式遥测仪对雄性野生型和GPR35基因敲除小鼠的血压进行了7-14天的监测。超声心动图评价心脏功能和大小，心肌细胞形态进行组织学评价。血管紧张素II(Ang II)输注2周，观察GPR35缺乏对病理生理状态的影响。用定量聚合酶链式反应检测心血管组织中Gpr35信使RNA的表达。与野生型小鼠相比，GPR35基因敲除小鼠的血压、心功能或心肌细胞形态没有显著差异。与野生型小鼠相比，注射Ang II后，GPR35基因敲除小鼠的收缩压、舒张压和平均动脉压显著升高，或左心室收缩功能受损。注射Ang II后，野生型小鼠心脏、肾脏和主动脉中Gpr35信使RNA的表达无显著差异。尽管GPR35似乎不影响基础心血管调节，但这些发现表明，它在Ang II诱导的高血压和心功能受损的发生发展中起着重要的病理作用。这表明GPR35是一种潜在的高血压治疗干预药物靶点。
The orphan receptor G protein–coupled receptor 35 (GPR35) has been associated with a range of diseases, including cancer, inflammatory bowel disease, diabetes, hypertension, and heart failure. To assess the potential for GPR35 as a therapeutic target in cardiovascular disease, this study investigated the cardiovascular phenotype of a GPR35 knockout mouse under both basal conditions and following pathophysiological stimulation. Blood pressure was monitored in male wild-type and GPR35 knockout mice over 7–14 days using implantable telemetry. Cardiac function and dimensions were assessed using echocardiography, and cardiomyocyte morphology evaluated histologically. Two weeks of angiotensin II (Ang II) infusion was used to investigate the effects of GPR35 deficiency under pathophysiological conditions. Gpr35 messenger RNA expression in cardiovascular tissues was assessed using quantitative polymerase chain reaction. There were no significant differences in blood pressure, cardiac function, or cardiomyocyte morphology in GPR35 knockout mice compared with wild-type mice. Following Ang II infusion, GPR35 knockout mice were protected from significant increases in systolic, diastolic, and mean arterial blood pressure or impaired left ventricular systolic function, in contrast to wild-type mice. There were no significant differences in Gpr35 messenger RNA expression in heart, kidney, and aorta following Ang II infusion in wild-type mice. Although GPR35 does not appear to influence basal cardiovascular regulation, these findings demonstrate that it plays an important pathological role in the development of Ang II–induced hypertension and impaired cardiac function. This suggests that GPR35 is a potential novel drug target for therapeutic intervention in hypertension.
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影响因子：
1.7
作者：
Surma M;Wei L;Shi J
通讯作者：
Shi J
影响因子：
5.6
作者：
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DOI：
10.1016/j.bbrc.2010.01.076
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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