Sudhir Rajni, Jaafar Nadim, Du Qingyou, Sukhodub Andriy, Jovanović Sofija, Kreouzi Magdalini, Jovanović Aleksandar
Department of Molecular and Clinical Medicine, University of Dundee, Dundee, Scotland, UK.
Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus.
J Basic Clin Physiol Pharmacol. 2021 Dec 3;33(5):619-624. doi: 10.1515/jbcpp-2021-0289. eCollection 2022 Sep 1.
SUR2A is an ABC protein serving as a regulatory subunit of ATP-sensitive (K) channels. An increase in SUR2A levels is cardioprotective and it is a potential therapeutic strategy against ischaemic heart disease, heart failure and other diseases. However, whether overexpression of this protein has any adverse effects is yet to be fully understood. Here, we examined the heart rate and the heart rate diurnal variation in mice overexpressing SUR2A (SUR2A+) and their littermate controls (WT) using ECG telemetry that was continuously recorded for 14 days (days 8-23 post-radiotransmitter implantation).
Using SigmaPlot 14.0 and Microsoft Excel, Area Under the Curve (AUC) for each parameter was calculated and plotted in a graph.
Both WT and SUR2A+ mice were more physically active during nights and there were no significant differences between two phenotypes. Physical activity was associated with increased heart rate in both phenotypes, but there were no differences in heart rate between phenotypes irrespective of physical activity or time of the day. A diurnal heart rate variation was preserved in the SUR2A+ mice. As area under the curve (AUC) analysis has the potential to reveal differences that are invisible with other statistical methods, we compared AUC of heart rate in SUR2A+ and WT mice. This analysis did not yield anything different from traditional analysis.
We conclude that increased SUR2A levels are not associated with changes in physical activity, heart rate and/or circadian rhythm influence on the heart rate. This lack of adverse effects supports a notion that manipulation with SUR2A levels is a promising cardioprotective strategy.
SUR2A是一种ABC蛋白，作为ATP敏感性钾通道的调节亚基。SUR2A水平升高具有心脏保护作用，是针对缺血性心脏病、心力衰竭和其他疾病的一种潜在治疗策略。然而，这种蛋白质的过表达是否有任何不良影响尚未完全了解。在此，我们使用心电图遥测技术，对过表达SUR2A的小鼠（SUR2A+）及其同窝对照小鼠（WT）的心率和心率昼夜变化进行了检测，连续记录14天（植入无线电发射器后第8 - 23天）。
使用SigmaPlot 14.0和Microsoft Excel软件，计算每个参数的曲线下面积（AUC）并绘制在图表中。
WT和SUR2A+小鼠在夜间的身体活动都更为活跃，两种表型之间没有显著差异。两种表型的身体活动都与心率增加有关，但无论身体活动或一天中的时间如何，两种表型之间的心率没有差异。SUR2A+小鼠保留了昼夜心率变化。由于曲线下面积（AUC）分析有可能揭示其他统计方法无法发现的差异，我们比较了SUR2A+和WT小鼠心率的AUC。该分析结果与传统分析没有任何不同。
我们得出结论，SUR2A水平升高与身体活动、心率和/或昼夜节律对心率的影响变化无关。这种缺乏不良影响支持了这样一种观点，即调节SUR2A水平是一种有前景的心脏保护策略。
