Deficiency of ataxia-telangiectasia mutated kinase attenuates Western-type diet-induced cardiac dysfunction in female mice.
Deficiency of ataxia-telangiectasia mutated kinase attenuates Western-type diet-induced cardiac dysfunction in female mice.
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DOI：
10.14814/phy2.15434
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发表时间：
2022-09
影响因子：
2.5
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中科院分区：
文献类型：
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长期食用西式饮食（WD）会导致心脏结构和功能异常。此前，我们已经证明，雄性 ATM（共济失调毛细血管扩张突变激酶）缺陷小鼠的 WD 摄入与体重（BW）加速增加、心脏收缩功能障碍（前负荷增加）以及肥厚、细胞凋亡和炎症加剧有关。本研究调查了 ATM 缺陷在 WD 诱导的雌性小鼠心脏功能和生化参数变化中的作用。将六周大的野生型 (WT) 和 ATM 杂合基因敲除 (hKO) 雌性小鼠置于 WD 或 NC（正常饲料）中 14 周。 WD 后 14 周测量体重增加、脂肪积累以及心脏功能和生化参数。与 hKO-WD 相比，WT-WD 中 WD 诱导的标准化至体重的皮下脂肪和总脂肪含量更高。使用超声心动图测量的心脏功能显示，与 WT-NC 相比，WT-WD 的缩短分数和射血分数百分比降低，左心室收缩末期直径和体积增加。与 hKO-NC 相比，hKO-WD 中的这些功能参数保持不变。与 WT-NC 相比，WT-WD 的心肌纤维化、心肌细胞肥大和细胞凋亡更高。然而，与 WT-WD 相比，hKO-WD 中的细胞凋亡显着较低，肥大显着较高。与 WT-NC 相比，WT-WD 中的 MMP-9 和 Bax 表达以及 Akt 激活更高。与 hKO-WD 相比，WT-WD 中的 PARP-1（全长）表达和 mTOR 激活较低。因此，雌性小鼠的 ATM 缺陷会减弱脂肪重量的增加，保留心脏功能，并与 WD 引起的心肌细胞凋亡减少相关。人类缺乏共济失调毛细血管扩张突变激酶（ATM）会增加患缺血性心脏病的风险。此前，我们提供的证据表明，雄性 ATM 缺陷小鼠的西式饮食会加速体重增加，诱导收缩功能障碍和前负荷增加，并加剧心脏肥大、细胞凋亡和炎症。在这里，我们提供的证据表明，ATM 缺乏与脂肪体重增加减弱有关，并在西式饮食喂养的雌性小鼠中发挥心脏保护作用，可保护心脏功能并减少心脏细胞凋亡。进一步研究 ATM 在西式饮食引起的心脏功能和结构变化中的性别特异性作用可能有助于阐明针对 ATM 缺乏症患者的适当的性别特异性治疗和营养咨询。
Chronic consumption of Western‐type diet (WD) induces cardiac structural and functional abnormalities. Previously, we have shown that WD consumption in male ATM (ataxia‐telangiectasia mutated kinase) deficient mice associates with accelerated body weight (BW) gain, cardiac systolic dysfunction with increased preload, and exacerbation of hypertrophy, apoptosis, and inflammation. This study investigated the role of ATM deficiency in WD‐induced changes in functional and biochemical parameters of the heart in female mice. Six‐week‐old wild‐type (WT) and ATM heterozygous knockout (hKO) female mice were placed on WD or NC (normal chow) for 14 weeks. BW gain, fat accumulation, and cardiac functional and biochemical parameters were measured 14 weeks post‐WD. WD‐induced subcutaneous and total fat contents normalized to body weight were higher in WT‐WD versus hKO‐WD. Heart function measured using echocardiography revealed decreased percent fractional shortening and ejection fraction, and increased LV end systolic diameter and volume in WT‐WD versus WT‐NC. These functional parameters remained unchanged in hKO‐WD versus hKO‐NC. Myocardial fibrosis, myocyte hypertrophy, and apoptosis were higher in WT‐WD versus WT‐NC. However, apoptosis was significantly lower and hypertrophy was significantly higher in hKO‐WD versus WT‐WD. MMP‐9 and Bax expression, and Akt activation were higher in WT‐WD versus WT‐NC. PARP‐1 (full‐length) expression and mTOR activation were lower in WT‐WD versus hKO‐WD. Thus, ATM deficiency in female mice attenuates fat weight gain, preserves heart function, and associates with decreased cardiac cell apoptosis in response to WD. Deficiency of ataxia telangiectasia mutated kinase (ATM) in humans increases the risk of ischemic heart disease. Previously, we provided evidence that Western‐type diet in male ATM deficient mice accelerates body weight gain, induces systolic dysfunction with increased preload, and exacerbates cardiac hypertrophy, apoptosis, and inflammation. Here, we provide evidence that ATM deficiency associates with attenuated fat weight gain, and plays a cardioprotective role with preservation of heart function and decreased cardiac cell apoptosis in female mice fed with Western‐type diet. Further investigations of sex‐specific role of ATM in Western‐type diet‐induced cardiac functional and structural changes may help elucidate the appropriate sex‐specific treatment and nutritional counseling for patients with ATM deficiency.
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影响因子：
5.4
作者：
Daniel LL;Daniels CR;Harirforoosh S;Foster CR;Singh M;Singh K
通讯作者：
Singh K
影响因子：
37.8
作者：
Abraham TM;Pedley A;Massaro JM;Hoffmann U;Fox CS
通讯作者：
Fox CS
影响因子：
3.5
作者：
Carbone, Salvatore;Mauro, Adolfo G.;Toldo, Stefano
通讯作者：
Toldo, Stefano
DOI：
10.1152/ajpheart.00319.2008
发表时间：
2008-09-01
影响因子：
4.8
作者：
Fang, Cindy X.;Dong, Feng;Ren, Jun
通讯作者：
Ren, Jun
影响因子：
4.3
作者：
Ballal, Kalpana;Wilson, Christopher R.;Harmancey, Romain;Taegtmeyer, Heinrich
通讯作者：
Taegtmeyer, Heinrich