Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, 06097, Halle, Germany.
Institut für Pharmakologie und Toxikologie, Martin-Luther-Universität Halle-Wittenberg, Medizinische Fakultät, Magdeburger Str. 4, 06112, Halle, Germany.
Mol Cell Biochem. 2022 Jun;477(6):1789-1801. doi: 10.1007/s11010-022-04407-2. Epub 2022 Mar 21.
Calsequestrin (CSQ2) is the main Ca-binding protein in the sarcoplasmic reticulum of the mammalian heart. In order to understand the function of calsequestrin better, we compared two age groups (young: 4-5 months of age versus adult: 18 months of age) of CSQ2 knock-out mice (CSQ2(-/-)) and littermate wild-type mice (CSQ2(+/+)). Using echocardiography, in adult mice, the basal left ventricular ejection fraction and the spontaneous beating rate were lower in CSQ2(-/-) compared to CSQ2(+/+). The increase in ejection fraction by β-adrenergic stimulation (intraperitoneal injection of isoproterenol) was lower in adult CSQ2(-/-) versus adult CSQ2(+/+). After hypoxia in vitro (isolated atrial preparations) by gassing the organ bath buffer with 95% N, force of contraction in electrically driven left atria increased to lower values in young CSQ2(-/-) than in young CSQ2(+/+). In addition, after global ischemia and reperfusion (buffer-perfused hearts according to Langendorff; 20-min ischemia and 15-min reperfusion), the rate of tension development was higher in young CSQ2(-/-) compared to young CSQ2(+/+). Finally, we evaluated signs of inflammation (immune cells, autoantibodies, and fibrosis). However, whereas no immunological alterations were found between all investigated groups, pronounced fibrosis was found in the ventricles of adult CSQ2(-/-) compared to all other groups. We suggest that in young mice, CSQ2 is important for cardiac performance especially in isolated cardiac preparations under conditions of impaired oxygen supply, but with differences between atrium and ventricle. Lack of CSQ2 leads age dependently to fibrosis and depressed cardiac performance in echocardiographic studies.
钙结合蛋白 2（CSQ2）是哺乳动物心脏肌浆网中的主要钙结合蛋白。为了更好地了解钙结合蛋白 2 的功能，我们比较了两个年龄组（年轻组：4-5 月龄与成年组：18 月龄）的 CSQ2 敲除小鼠（CSQ2(-/-)）和同窝野生型小鼠（CSQ2(+/+)）。通过超声心动图检查，在成年小鼠中，CSQ2(-/-)的左心室基础射血分数和自发性心率均低于 CSQ2(+/+)。β-肾上腺素能刺激（腹腔注射异丙肾上腺素）引起的射血分数增加，成年 CSQ2(-/-)低于成年 CSQ2(+/+)。在体外缺氧（通过向器官浴缓冲液中鼓入 95% N2 制备分离的心房制剂）后，电驱动的左心房收缩力在年轻的 CSQ2(-/-)中比在年轻的 CSQ2(+/+)中增加到更低的值。此外，在整体缺血和再灌注（根据 Langendorff 进行缓冲液灌注的心脏；20 分钟缺血和 15 分钟再灌注）后，年轻的 CSQ2(-/-)的张力发展速度高于年轻的 CSQ2(+/+)。最后，我们评估了炎症迹象（免疫细胞、自身抗体和纤维化）。然而，尽管所有研究组之间均未发现免疫改变，但成年 CSQ2(-/-)的心室中发现了明显的纤维化，与所有其他组相比均有差异。我们认为，在年轻小鼠中，CSQ2 对心脏功能尤其是在缺氧供应受损的情况下的离体心脏制剂中非常重要，但心房和心室之间存在差异。缺乏 CSQ2 会导致依赖年龄的纤维化，并在超声心动图研究中导致心脏功能下降。
