Cardiac magnetic resonance assessment of interstitial myocardial fibrosis and cardiomyocyte hypertrophy in hypertensive mice treated with spironolactone.
Cardiac magnetic resonance assessment of interstitial myocardial fibrosis and cardiomyocyte hypertrophy in hypertensive mice treated with spironolactone.
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DOI：
10.1161/jaha.114.000790
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发表时间：
2014-06-25
影响因子：
5.4
通讯作者：
Jerosch-Herold M
中科院分区：
文献类型：
--
作者：
Coelho-Filho OR;Shah RV;Neilan TG;Mitchell R;Moreno H Jr;Kwong R;Jerosch-Herold M
近50%的心力衰竭患者保留了左心室射血分数，间质纤维化和心肌细胞肥大是压力超负荷的早期表现。然而，缺乏通过治疗动态和非侵入性地评估组织特征的方法。我们利用心脏磁共振(CMR)测量了盐皮质激素受体阻断对LV压力超负荷时组织表型的影响。将小鼠随机分为L硝基ω甲酯组(L NAME，3 mg/mL水溶液，n=22)或L NAME加螺内酯(50 mg/kg/d，皮下注射；n=21)。心肌细胞外体积(ECV；弥漫性间质纤维化标志物)和细胞内水寿命(τic；心肌肥大标志物)在基础状态和治疗7周后结合组织学评估用CMRT1显像法测定。给予L-NAME诱导的小鼠高血压心脏病，与安慰剂对照组相比，平均动脉压、左心室重量、ECV和τ增加，而左心室射血分数保持(>；50%)。与之相比，同时给予螺内酯和L-NAME(“L-NAME+S”)的动物表现出较少的向心性重构，较低的心肌ECV和τic，表明间质纤维化和心肌细胞肥大减少(L-NAME组ECV0.43±0.09vs L-NAME+S组0.25±0.03，P<；0.001；τIC：L-NAME组0.42±0.11比L-NAME+S组0.12±0.05)。在7周时，L-NAME和螺内酯联合治疗的小鼠与安慰剂治疗的对照组相似。螺内酯可减轻高血压性心脏病患者的间质纤维化和心肌细胞肥大。CMR可以在压力超负荷时对心肌组织重塑进行表型，进一步加深了我们对心力衰竭进展的理解。
Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Mice were randomized to l‐nitro‐ω‐methyl ester (l‐NAME, 3 mg/mL in water; n=22), or l‐NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l‐NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo‐treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l‐NAME (“l‐NAME+S”) showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43±0.09 for l‐NAME versus 0.25±0.03 for l‐NAME+S, P<0.001; τic: 0.42±0.11 for l‐NAME groups versus 0.12±0.05 for l‐NAME+S group). Mice treated with a combination of l‐NAME and spironolactone were similar to placebo‐treated controls at 7 weeks. Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure‐overload, furthering our understanding of HF progression.