Cadmium exposure induces a sex-dependent decline in left ventricular cardiac function.
Cadmium exposure induces a sex-dependent decline in left ventricular cardiac function.
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DOI：
10.1016/j.lfs.2023.121712
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发表时间：
2023-04
期刊：
影响因子：
6.1
通讯作者：
Michael Fitch;Raihan Kabir;Obialunanma V. Ebenebe;Nicole Taube;Haley Garbus;P. Sinha;Nadan Wang;Sumita Mishra;B. Lin;Grace K. Muller;Mark J. Kohr
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文献类型：
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作者：
Michael Fitch;Raihan Kabir;Obialunanma V. Ebenebe;Nicole Taube;Haley Garbus;P. Sinha;Nadan Wang;Sumita Mishra;B. Lin;Grace K. Muller;Mark J. Kohr
目的镉暴露是一个世界性的问题，与心血管疾病的发展有关。本研究旨在阐明慢性镉暴露对心脏结构和功能影响的机制细节。主要方法雄性和雌性小鼠通过饮水染毒8周。进行了一系列超声心动图和血压测量。我们评估了肥厚和纤维化的标记物，以及处理钙离子的分子指标。关键发现：接触氯化镉后，男性的左心室射血分数和短轴缩短率显著降低，收缩末期的心室容量增加，收缩末期的室间隔厚度减少。有趣的是，在女性身上没有检测到变化。在分离的心肌细胞上的实验表明，氯化镉引起的收缩功能障碍也存在于细胞水平，表现为随着氯化镉的暴露，钙瞬变和肌节缩短幅度减少。进一步的机制研究发现，在接触氯化镉的男性心脏中，肌浆网/内质网钙-ATPase 2a(SERCA2a)蛋白表达和磷酸化蛋白水平下降。意义我们的新研究结果为镉暴露如何作为心血管疾病的性别特异性驱动因素提供了重要的见解，并进一步强调了减少人类镉暴露的重要性。
AimsCadmium exposure is a worldwide problem that has been linked to the development of cardiovascular disease. This study aimed to elucidate mechanistic details of chronic cadmium exposure on the structure and function of the heart.Main methodsMale and female mice were exposed to cadmium chloride (CdCl2) via drinking water for eight weeks. Serial echocardiography and blood pressure measurements were performed. Markers of hypertrophy and fibrosis were assessed, along with molecular targets of Ca2+-handling.Key findingsMales exhibited a significant reduction in left ventricular ejection fraction and fractional shortening with CdCl2exposure, along with increased ventricular volume at end-systole, and decreased interventricular septal thickness at end-systole. Interestingly, no changes were detected in females. Experiments in isolated cardiomyocytes revealed that CdCl2-induced contractile dysfunction was also present at the cellular level, showing decreased Ca2+transient and sarcomere shortening amplitude with CdCl2exposure. Further mechanistic investigation uncovered a decrease in sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) protein expression and phosphorylated phospholamban levels in male hearts with CdCl2exposure.SignificanceThe findings of our novel study provide important insight into how cadmium exposure may act as a sex-specific driver of cardiovascular disease, and further underscore the importance of reducing human exposure to cadmium.