Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI United States of America.
Bone and Joint Center, Henry Ford Health System, Detroit, MI United States of America.
PLoS One. 2018 Apr 20;13(4):e0195796. doi: 10.1371/journal.pone.0195796. eCollection 2018.
E487K point mutation of aldehyde dehydrogenase (ALDH) 2 (ALDH22) in East Asians intrinsically lowers ALDH2 activity. ALDH22 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 ALDH22 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 ALDH22 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 ALDH22 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 ALDH22 mice with diabetes compared to C57BL/6 diabetic mice as well as non-diabetic (control) ALDH22 mice. The diabetic ALDH22 mice also exhibited poor maximal running speed and distance. Our data suggest that high-fat fed diabetic ALDH22 mice exhibit HFpEF and treadmill exercise stress echo test is able to determine this HFpEF in the diabetic ALDH22 mice.
东亚人中醛脱氢酶（ALDH）2 的 E487K 点突变（ALDH22）从本质上降低了 ALDH2 的活性。ALDH22 与糖尿病性心肌病有关。糖尿病患者表现出射血分数保留的心力衰竭（HFpEF），即尽管他们的收缩功能保持正常，但可能表现出舒张功能障碍，暗示心肌健康受到威胁。目前，在糖尿病小鼠中检测心脏功能恶化具有挑战性。临床设置中的应变成像（echo）是一种用于测量冠状动脉疾病中心脏储备和心脏功能障碍的程序。因此，我们假设高脂肪饮食喂养的 2 型糖尿病 ALDH22 突变小鼠表现出 HFpEF，这可以通过心脏回声应激测试方法来测量。我们通过高脂肪饮食诱导 12 周龄雄性 C57BL/6 和 ALDH22 小鼠发生 2 型糖尿病。在 DM 诱导 4 个月后，我们通过清醒应变成像测量糖尿病和对照 C57BL/6 和 ALDH22 基因型小鼠的心脏功能。随后，我们让小鼠在跑步机上跑步直到精疲力竭，施加运动应激。应激后，我们再次测量它们的心脏功能。只有在跑步机跑步后，而不是在休息时，我们发现与 C57BL/6 糖尿病小鼠以及非糖尿病（对照）ALDH22 小鼠相比，糖尿病 ALDH22 小鼠的 %短轴缩短率和 %射血分数显着下降。糖尿病 ALDH22 小鼠的最大跑步速度和距离也较差。我们的数据表明，高脂肪饮食喂养的糖尿病 ALDH22 小鼠表现出 HFpEF，跑步机运动应激回声测试能够确定糖尿病 ALDH22 小鼠的这种 HFpEF。
