Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart
Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart
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DOI：
10.1096/fj.04-2263com
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发表时间：
2004-11-01
期刊：
影响因子：
4.8
通讯作者：
Taegtmeyer, H
中科院分区：
文献类型：
--
作者：
Sharma, S;Adrogue, JV;Taegtmeyer, H
在脂肪毒性的动物模型中，甘油三酯在心肌细胞内的积累与收缩功能障碍有关。然而，心肌内脂肪沉积是否是人类心力衰竭的一个特征仍有待确定。我们假设，心肌内脂肪堆积是非缺血性心力衰竭的共同特征，并与基因表达的变化有关，类似于在脂肪毒性动物模型中发现的变化。对27例(9例女性)非缺血性心力衰竭患者的心肌组织进行油红O染色和基因表达分析。我们测定了6只Zucker糖尿病肥胖(ZDF)和6只Zucker瘦(ZL)大鼠的心肌内脂质、基因表达和收缩功能。30%的非缺血性衰竭心脏存在心肌内脂质过载。糖尿病和肥胖症患者的脂质染色水平最高(BMI>；30)。心肌内脂质沉积与过氧化体增殖物激活受体α(PPARpha)调节的基因、肌球蛋白重链β(MHC-β)和肿瘤坏死因子α(TNF-α)上调有关。ZDF大鼠心脏中的心肌内脂质超载与收缩功能障碍和基因表达的变化有关，这些变化类似于在脂质超载的衰竭的人类心脏中发现的变化。我们的发现确定了一组心力衰竭和严重代谢紊乱的患者，其特征是心肌内甘油三酯超载和与收缩功能障碍相关的基因表达变化。
In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accumulation is a common feature of non-ischemic heart failure and is associated with changes in gene expression similar to those found in an animal model of lipotoxicity. Intramyocardial lipid staining with oil red O and gene expression analysis was performed on heart tissue from 27 patients (9 female) with non-ischemic heart failure. We determined intramyocardial lipid, gene expression, and contractile function in hearts from 6 Zucker diabetic fatty (ZDF) and 6 Zucker lean (ZL) rats. Intramyocardial lipid overload was present in 30% of non-ischemic failing hearts. The highest levels of lipid staining were observed in patients with diabetes and obesity (BMI>30). Intramyocardial lipid deposition was associated with an up-regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) -regulated genes, myosin heavy chain beta (MHC-beta), and tumor necrosis factor alpha (TNF-alpha). Intramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and changes in gene expression similar to changes found in failing human hearts with lipid overload. Our findings identify a subgroup of patients with heart failure and severe metabolic dysregulation characterized by intramyocardial triglyceride overload and changes in gene expression that are associated with contractile dysfunction.