Type-2 diabetic aldehyde dehydrogenase 2 mutant mice (ALDH 2*2) exhibiting heart failure with preserved ejection fraction phenotype can be determined by exercise stress echocardiography.
Type-2 diabetic aldehyde dehydrogenase 2 mutant mice (ALDH 2*2) exhibiting heart failure with preserved ejection fraction phenotype can be determined by exercise stress echocardiography.
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DOI：
10.1371/journal.pone.0195796
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Palaniyandi SS
中科院分区：
文献类型：
--
作者：
Pan G;Munukutla S;Kar A;Gardinier J;Thandavarayan RA;Palaniyandi SS
在东亚人中，乙醛脱氢酶（ALDH）2（ALDH 2 *2）的E487 K点突变本质上降低了ALDH 2活性。ALDH 2 *2与糖尿病心肌病有关。糖尿病患者表现出射血分数保留的心力衰竭（HFpEF），即，虽然他们的收缩期心脏功能被保留，但他们可能表现出舒张期功能障碍，这意味着心肌健康受到危害。目前，检测糖尿病小鼠的心脏功能恶化具有挑战性。负荷超声心动图（echo）在临床上是一种用于测量冠状动脉疾病患者的心脏储备和受损心脏功能的程序。因此，我们假设高脂饮食喂养的2型糖尿病ALDH 2 *2突变小鼠表现出HFpEF，其可以通过心脏回波负荷试验方法测量。我们通过高脂饮食在12周龄雄性C57 BL/6和ALDH 2 *2小鼠中诱导2型糖尿病。在糖尿病诱导4个月结束时，我们用意识超声检测了C57 BL/6和ALDH 2 *2基因型糖尿病小鼠和对照小鼠的心功能。随后，我们通过让小鼠在跑步机上跑步直到筋疲力尽来施加运动应激。应激后，我们再次测量了他们的心脏功能。仅在跑步机跑步后，而不是在休息时，我们发现与C57 BL/6糖尿病小鼠以及非糖尿病（对照）ALDH 2 *2小鼠相比，患有糖尿病的ALDH 2 *2小鼠的缩短率%和射血分数%显著降低。糖尿病ALDH 2 *2小鼠也表现出较差的最大跑步速度和距离。我们的数据表明，高脂肪喂养的糖尿病ALDH 2 *2小鼠表现出HFpEF，并且跑步机运动负荷超声心动图测试能够确定糖尿病ALDH 2 *2小鼠中的这种HFpEF。
E487K point mutation of aldehyde dehydrogenase (ALDH) 2 (ALDH2*2) in East Asians intrinsically lowers ALDH2 activity. ALDH2*2 is associated with diabetic cardiomyopathy. Diabetic patients exhibit heart failure of preserved ejection fraction (HFpEF) i.e. while the systolic heart function is preserved in them, they may exhibit diastolic dysfunction, implying a jeopardized myocardial health. Currently, it is challenging to detect cardiac functional deterioration in diabetic mice. Stress echocardiography (echo) in the clinical set-up is a procedure used to measure cardiac reserve and impaired cardiac function in coronary artery diseases. Therefore, we hypothesized that high-fat diet fed type-2 diabetic ALDH2*2 mutant mice exhibit HFpEF which can be measured by cardiac echo stress test methodology. We induced type-2 diabetes in 12-week-old male C57BL/6 and ALDH2*2 mice through a high-fat diet. At the end of 4 months of DM induction, we measured the cardiac function in diabetic and control mice of C57BL/6 and ALDH2*2 genotypes by conscious echo. Subsequently, we imposed exercise stress by allowing the mice to run on the treadmill until exhaustion. Post-stress, we measured their cardiac function again. Only after treadmill running, but not at rest, we found a significant decrease in % fractional shortening and % ejection fraction in ALDH2*2 mice with diabetes compared to C57BL/6 diabetic mice as well as non-diabetic (control) ALDH2*2 mice. The diabetic ALDH2*2 mice also exhibited poor maximal running speed and distance. Our data suggest that high-fat fed diabetic ALDH2*2 mice exhibit HFpEF and treadmill exercise stress echo test is able to determine this HFpEF in the diabetic ALDH2*2 mice.
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