Blockade of hypoxia-caused nonmyocytes apoptosis helps improve survival and mitigate ventricular remodeling and dysfunction during the chronic stage of myocardial infarction. But tools affecting nonmyocyte apoptosis are very rare. Sphingosylphosphorylcholine (SPC), a naturally occurring bioactive sphingolipid in plasma, was proved to protect cardiomyocyte against apoptosis in an ischemic model in our previous study. Here, we showed that SPC also inhibited hypoxia-induced apoptosis in myofibroblasts, an important type of nonmyocytes in the heart. Calmodulin (CaM) is an identified receptor of SPC. We clarified that SPC inhibited myofibroblast apoptosis through CaM as evidenced by decreased cleaved caspase 3, PARP1 and condensed nucleus. Furthermore, the employment of inhibitor and agonist of p38 and STAT3 suggests that SPC inhibits myofibroblast apoptosis by regulating the phosphorylation of p38 and STAT3, and they act as downstream of CaM. The present work may provide new evidence on the regulation of myofibroblasts apoptosis by SPC and a novel target for heart remodeling after hypoxia.

在心肌梗死的慢性阶段，阻断缺氧引起的非肌细胞凋亡有助于提高存活率并减轻心室重构和功能障碍。但是影响非肌细胞凋亡的工具非常罕见。鞘氨醇磷酰胆碱 (SPC) 是血浆中一种天然存在的生物活性鞘脂，在我们之前的研究中被证明可以保护心肌细胞免受缺血模型中的细胞凋亡。在这里，我们发现 SPC 还抑制肌成纤维细胞中缺氧诱导的细胞凋亡，肌成纤维细胞是心脏中一种重要的非肌细胞。钙调蛋白 (CaM) 是一种已识别的 SPC 受体。我们澄清了 SPC 通过 CaM 抑制肌成纤维细胞凋亡，如裂解的半胱天冬酶 3、PARP1 和凝聚核减少所证明的那样。此外，p38 和 STAT3 抑制剂和激动剂的应用表明 SPC 通过调节 p38 和 STAT3 的磷酸化来抑制肌成纤维细胞凋亡，并且它们充当 CaM 的下游。目前的工作可能为 SPC 调节肌成纤维细胞凋亡提供新的证据，并为缺氧后心脏重塑提供新的靶点。