Influence of Age on Hyperoxia-Induced Cardiac Pathophysiology in Type 1 Diabetes Mellitus (T1DM) Mouse Model.
Influence of Age on Hyperoxia-Induced Cardiac Pathophysiology in Type 1 Diabetes Mellitus (T1DM) Mouse Model.
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DOI：
10.3390/cells12111457
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发表时间：
2023-05-24
期刊：
影响因子：
6
通讯作者：
Panguluri, Siva Kumar
中科院分区：
文献类型：
--
作者：
Saleem, Faizan;Mansour, Hussein;Vichare, Riddhi;Ayalasomayajula, Yashwant;Yassine, Jenna;Hesaraghatta, Anagha;Panguluri, Siva Kumar
关键词：
机械通气通常会导致高氧血症，这种情况的特征是 SpO2 水平过高 (>96%)。高氧会导致生理参数的变化、严重的心脏重塑、心律失常以及心脏离子通道的改变，所有这些都可能导致患心血管疾病 (CVD) 的风险逐渐增加。这项研究扩展了我们之前对年轻秋田小鼠所做的工作的分析，该研究表明，与野生型 (WT) 小鼠相比，暴露于高氧环境会使 1 型糖尿病小鼠模型的心脏结果恶化。年龄是一个独立的危险因素，当存在主要合并症（例如 1 型糖尿病 (T1D)）时，可能会进一步恶化心脏结局。因此，本研究将老年 T1D 秋田小鼠置于临床高氧环境中，并分析了心脏结果。总体而言，与年轻的秋田小鼠相比，老年秋田小鼠（60 至 68 周）预先存在心脏问题。老年小鼠体重超重，心脏横截面积增加，QTc 和 JT 间期延长，这些被认为是室内心律失常等 CVD 的主要危险因素。此外，暴露于高氧环境会导致这些啮齿动物发生严重的心脏重塑以及 Kv 4.2 和 KChIP2 心脏钾通道的减少。根据性别差异，老年雄性秋田小鼠比老年雌性小鼠心脏结果不良的风险更高。即使在基线常氧暴露下，老年雄性秋田小鼠的 RR、QTc 和 JT 间期也延长。此外，它们无法通过适应性心脏肥大来抵御高氧应激，这至少在某种程度上是由于心脏雄激素受体减少所致。这项针对老年秋田小鼠的研究旨在引起人们对临床上重要但尚未充分研究的课题的关注，即在先前存在合并症的情况下高氧对心脏参数的影响。这些发现将有助于修改对入住 ICU 的老年 T1D 患者的护理服务。
Mechanical ventilation often results in hyperoxia, a condition characterized by excess SpO2 levels (>96%). Hyperoxia results in changes in the physiological parameters, severe cardiac remodeling, arrhythmia development, and alteration of cardiac ion channels, all of which can point toward a gradual increase in the risk of developing cardiovascular disease (CVD). This study extends the analysis of our prior work in young Akita mice, which demonstrated that exposure to hyperoxia worsens cardiac outcomes in a type 1 diabetic murine model as compared to wild-type (WT) mice. Age is an independent risk factor, and when present with a major comorbidity, such as type 1 diabetes (T1D), it can further exacerbate cardiac outcomes. Thus, this research subjected aged T1D Akita mice to clinical hyperoxia and analyzed the cardiac outcomes. Overall, aged Akita mice (60 to 68 weeks) had preexisting cardiac challenges compared to young Akita mice. Aged mice were overweight, had an increased cardiac cross-sectional area, and showed prolonged QTc and JT intervals, which are proposed as major risk factors for CVD like intraventricular arrhythmias. Additionally, exposure to hyperoxia resulted in severe cardiac remodeling and a decrease in Kv 4.2 and KChIP2 cardiac potassium channels in these rodents. Based on sex-specific differences, aged male Akita mice had a higher risk of poor cardiac outcomes than aged females. Aged male Akita mice had prolonged RR, QTc, and JT intervals even at baseline normoxic exposure. Moreover, they were not protected against hyperoxic stress through adaptive cardiac hypertrophy, which, at least to some extent, is due to reduced cardiac androgen receptors. This study in aged Akita mice aims to draw attention to the clinically important yet understudied subject of the effect of hyperoxia on cardiac parameters in the presence of preexisting comorbidities. The findings would help revise the provision of care for older T1D patients admitted to ICUs.
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影响因子：
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作者：
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通讯作者：
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DOI：
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