The cardiac (pro)renin receptor is primarily expressed in myocyte transverse tubules and is increased in experimental diabetic cardiomyopathy
The cardiac (pro)renin receptor is primarily expressed in myocyte transverse tubules and is increased in experimental diabetic cardiomyopathy
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DOI：
10.1097/hjh.0b013e3283462674
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发表时间：
2011-06-01
影响因子：
4.9
通讯作者：
Gilbert, Richard E.
中科院分区：
文献类型：
--
作者：
Connelly, Kim A.;Advani, Andrew;Gilbert, Richard E.
肾素原受体是一种350个氨基酸的跨膜蛋白，它通过配体结合，提高了肾素和肾素对血管紧张素原裂解的催化效率，增加了细胞表面血管紧张素I的形成。虽然与广泛的疾病有关，但迄今为止的研究主要集中在肾脏，特别是糖尿病方面。我们试图检查心脏中肾素受体的位点特异性表达。方法利用共聚焦显微镜、位点特异性标记和透射电镜，我们在细胞/亚细胞水平上评估了pro（肾素）受体在心脏中的位置。我们使用糖尿病心肌病的TGR[m(Ren2)-27]模型和直接肾素抑制剂aliskiren，评估了疾病和肾素-血管紧张素系统阻断情况下pro（肾素）受体的表达。结果前肾素受体主要分布在心肌细胞的z盘和二盘，与空泡H+- atp酶和赖胺受体分布密切一致，分别位于t小管和肌浆网末端池内。糖尿病大鼠心脏Pro（肾素）受体mRNA/蛋白丰度增加约3倍，与舒张功能障碍、心肌细胞肥大和间质纤维化有关
Background The pro(renin) receptor is a 350 amino acid transmembrane protein, that on ligand binding, increases the catalytic efficiency of angiotensinogen cleavage by both prorenin and renin, augmenting angiotensin I formation at the cell surface. While implicated in a broad range of diseases, studies to date have focused on the kidney, particularly in the diabetic context. We sought to examine the site-specific expression of the pro(renin) receptor within the heart.Methods Using confocal microscopy, site-specific markers and transmission electron microscopy we assessed the location of the pro(renin) receptor in the heart at both cellular/sub-cellular levels. We assessed pro(renin) receptor expression in the setting of disease and blockade of the renin-angiotensin system, using the TGR[m(Ren2)-27] model of diabetic cardiomyopathy and the direct renin inhibitor, aliskiren.Results The pro(renin) receptor was found predominantly at the Z-disc and dyad of cardiac myocytes coinciding closely with the distributions of the vacuolar H+-ATPase and ryanodine receptor, known to be located within T-tubules and the sarcoplasmic reticulum's terminal cisternae, respectively. Pro(renin) receptor mRNA/protein abundance were increased similar to 3-fold in the hearts of diabetic rats in association with diastolic dysfunction, myocyte hypertrophy and interstitial fibrosis (all P