Sex-specific impact of aldosterone receptor antagonism on ventricular remodeling and gene expression after myocardial infarction.
Sex-specific impact of aldosterone receptor antagonism on ventricular remodeling and gene expression after myocardial infarction.
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醛固酮受体拮抗作用对心肌梗塞后心室重塑和基因表达的性别特异性影响。
DOI：
10.1111/j.1752-8062.2009.00094.x
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Hare JM
中科院分区：
文献类型：
--
作者：
Kanashiro-Takeuchi RM;Heidecker B;Lamirault G;Dharamsi JW;Hare JM
醛固酮受体拮抗剂可降低死亡率并改善心肌梗死（MI）后重塑。由于醛固酮和雌激素信号通路相互作用，我们假设醛固酮阻断是性别特异性的。因此，我们研究了依普利酮对左心室（LV）重构和基因表达的影响，男性梗死大鼠与女性梗死大鼠。MI和假手术动物在术后3天随机接受依普利酮（100 mg/kg/天）或安慰剂，持续4周，并通过超声心动图进行评估。在MI安慰剂组中，两种性别的左心室舒张末期尺寸（LVEDD）从7.3 ± 0.4 mm增加到10.2 ± 1.0 mm（p < 0.05），射血分数（EF）从82.3 ± 4%下降到45.5 ± 11%（p < 0.05）（组间p = NS）。依普利酮在女性（8.8 ± 0.2 mm，p < 0.05 vs.安慰剂）中比在男性（9.7 ± 0.2 mm，p = NS vs.安慰剂）中更有效地减弱LVEDD扩大，并且在女性中改善EF（56.7 ± 3%，p < 0.05 vs.安慰剂），但在男性中没有改善EF（50.6 ± 3%，p = NS vs.安慰剂）。使用Rat_230 - 2.0微阵列（Affyellow）的转录组学分析显示，在女性中，MI后19%的下调基因和44%的上调基因通过依普利酮恢复正常。相比之下，依普利酮仅恢复了男性中4%的过度表达基因。总之，这些数据表明，醛固酮阻断减少MI诱导的心脏重塑和基因表达的表型改变，优先在女性比男性。使用转录组签名检测女性中依普利酮的更大益处对个性化医疗具有潜在意义。
Aldosterone receptor antagonism reduces mortality and improves post-myocardial infarction (MI) remodeling. Because aldosterone and estrogen signaling pathways interact, we hypothesized that aldosterone blockade is sex-specific. Therefore, we investigated the impact of eplerenone on left ventricular (LV) remodeling and gene expression of male infarcted rats versus female infarcted rats. MI and Sham animals were randomized to receive eplerenone (100 mg/kg/day) or placebo 3 days post-surgery for 4 weeks and assessed by echocardiography. In the MI placebo group, left ventricular end-diastolic dimension (LVEDD) increased from 7.3 ± 0.4 mm to 10.2 ± 1.0 mm (p < 0.05) and ejection fraction (EF) decreased from 82.3 ± 4% to 45.5 ± 11% (p < 0.05) in both sexes (p = NS between groups). Eplerenone attenuated LVEDD enlargement more effectively in females (8.8 ± 0.2 mm, p < 0.05 vs. placebo) than in males (9.7 ± 0.2 mm, p = NS vs. placebo) and improved EF in females (56.7 ± 3%, p < 0.05 vs. placebo) but not in males (50.6 ± 3%, p = NS vs. placebo). Transcriptomic analysis using Rat_230−2.0 microarrays (Affymetrix) revealed that in females 19% of downregulated genes and 44% of upregulated genes post-MI were restored to normal by eplerenone. In contrast, eplerenone only restored 4% of overexpressed genes in males. Together, these data suggest that aldosterone blockade reduces MI-induced cardiac remodeling and phenotypic alterations of gene expression preferentially in females than in males. The use of transcriptomic signatures to detect greater benefit of eplerenone in females has potential implications for personalized medicine.
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影响因子：
10.8
作者：
Kluge, A;Zimmermann, R;Schaper, W
通讯作者：
Schaper, W
DOI：
10.1152/ajpheart.2001.281.2.h647
发表时间：
2001-08-01
影响因子：
4.8
作者：
Delyani, JA;Robinson, EL;Rudolph, AE
通讯作者：
Rudolph, AE
影响因子：
20.1
作者：
PFEFFER, MA;PFEFFER, JM;BRAUNWALD, E
通讯作者：
BRAUNWALD, E
影响因子：
46.9
作者：
Canales, Roger D.;Luo, Yuling;Goodsaid, Federico M.
通讯作者：
Goodsaid, Federico M.
影响因子：
37.8
作者：
Hayashi, M;Tsutamoto, T;Horie, M
通讯作者：
Horie, M