Gravez Basile, Tarjus Antoine, Pelloux Véronique, Ouvrard-Pascaud Antoine, Delcayre Claude, Samuel Janelise, Clément Karine, Farman Nicolette, Jaisser Fréderic, Messaoudi Smail
Inserm U1138, Team 1, 15 rue de l'école de médecine, Paris, France (B.G., A.T., N.F., F.J., S.M.).
INSERM-UMR 1166 Team 6- GH Pitié-Salpêtrière, 83 Bd de l'hôpital, Paris, France (P., K.C.).
J Am Heart Assoc. 2015 Jan 6;4(1):e001266. doi: 10.1161/JAHA.114.001266.
Experimentally, aldosterone in association with NaCl induces cardiac fibrosis, oxidative stress, and inflammation through mineralocorticoid receptor activation; however, the biological processes regulated by aldosterone alone in the heart remain to be identified.
Mice were treated for 7 days with aldosterone, and then cardiac transcriptome was analyzed. Aldosterone regulated 60 transcripts (51 upregulated and 9 downregulated) in the heart (fold change ≥1.5, false discovery rate <0.01). To identify the biological processes modulated by aldosterone, a gene ontology analysis was performed. The majority of aldosterone-regulated genes were involved in cell division. The cardiac Ki-67 index (an index of proliferation) of aldosterone-treated mice was higher than that of nontreated mice, confirming microarray predictions. Costaining of Ki-67 with vinculin, CD68, α-smooth muscle actin, CD31, or caveolin 1 revealed that the cycling cells were essentially endothelial cells. Aldosterone-induced mineralocorticoid receptor-dependent proliferation was confirmed ex vivo in human endothelial cells. Moreover, pharmacological-specific blockade of mineralocorticoid receptor by eplerenone inhibited endothelial cell proliferation in a preclinical model of heart failure (transverse aortic constriction).
Aldosterone modulates cardiac gene expression and induces the proliferation of cardiac endothelial cells in vivo.
在实验中，醛固酮与氯化钠联合作用通过激活盐皮质激素受体诱导心脏纤维化、氧化应激和炎症；然而，心脏中仅由醛固酮调节的生物学过程仍有待确定。
用醛固酮处理小鼠7天，然后分析心脏转录组。醛固酮调节心脏中的60个转录本（51个上调和9个下调）（变化倍数≥1.5，错误发现率<0.01）。为了确定醛固酮调节的生物学过程，进行了基因本体分析。大多数醛固酮调节的基因参与细胞分裂。醛固酮处理小鼠的心脏Ki-67指数（增殖指数）高于未处理小鼠，证实了微阵列预测。Ki-67与纽蛋白、CD68、α-平滑肌肌动蛋白、CD31或小窝蛋白1的共染色显示，循环细胞主要是内皮细胞。醛固酮诱导的盐皮质激素受体依赖性增殖在人内皮细胞中得到离体证实。此外，依普利酮对盐皮质激素受体的药理学特异性阻断在心力衰竭临床前模型（主动脉缩窄）中抑制了内皮细胞增殖。
醛固酮在体内调节心脏基因表达并诱导心脏内皮细胞增殖。
