Deoxycorticosterone Acetate/Salt-Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure
Deoxycorticosterone Acetate/Salt-Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure
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DOI：
10.1161/hypertensionaha.115.06530
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发表时间：
2016-01-01
期刊：
影响因子：
8.3
通讯作者：
Hein, Lutz
中科院分区：
文献类型：
--
作者：
Lother, Achim;Fuerst, David;Hein, Lutz
慢性肾病的患病率急剧增加，需要新的治疗方法。盐皮质激素受体（MR）拮抗剂已被证明在心脏疾病的治疗中非常有益。导致心脏炎症和重塑的细胞和分子事件被认为与介导肾损伤的事件相似。因此，本研究旨在评估和直接比较内皮细胞MR缺失对醋酸脱氧皮质酮诱导的高血压模型中心脏和肾脏损伤的影响。内皮MR缺失改善醋酸脱氧皮质酮/盐诱导的心脏重塑。这与MR缺陷的心脏内皮细胞中血管细胞粘附分子Vcam 1的表达减少有关。动态血压遥测显示MR缺失的保护作用与血压无关。与心脏相似，醋酸去氧皮质酮/盐诱导了严重的肾损伤，包括炎症、纤维化、肾小球损伤和蛋白尿。然而，没有观察到基因型之间的肾损伤的差异。总之，内皮细胞的MR缺失改善了醋酸脱氧皮质酮/盐诱导的心脏炎症和重塑，独立于血压的改变，但不影响肾损伤。这些发现表明，内皮细胞MR缺失后介导器官保护的抗炎机制对心脏和肾脏具有特异性。
Chronic kidney disease has a tremendously increasing prevalence and requires novel therapeutic approaches. Mineralocorticoid receptor (MR) antagonists have proven highly beneficial in the therapy of cardiac disease. The cellular and molecular events leading to cardiac inflammation and remodeling are proposed to be similar to those mediating renal injury. Thus, this study was designed to evaluate and directly compare the effect of MR deletion in endothelial cells on cardiac and renal injury in a model of deoxycorticosterone acetate-induced hypertension. Endothelial MR deletion ameliorated deoxycorticosterone acetate/salt-induced cardiac remodeling. This was associated with a reduced expression of the vascular cell adhesion molecule Vcam1 in MR-deficient cardiac endothelial cells. Ambulatory blood pressure telemetry revealed that the protective effect of MR deletion was independent from blood pressure. Similar to the heart, deoxycorticosterone acetate/salt-induced severe renal injury, including inflammation, fibrosis, glomerular injury, and proteinuria. However, no differences in renal injury were observed between genotypes. In conclusion, MR deletion from endothelial cells ameliorated deoxycorticosterone acetate/salt-induced cardiac inflammation and remodeling independently from alterations in blood pressure but it did not affect renal injury. These findings suggest that the anti-inflammatory mechanism mediating organ protection after endothelial cell MR deletion is specific for the heart versus the kidney.