Department of Physiology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, 230-8501, Japan.
Department of Periodontology, Tsurumi University School of Dental Medicine, Yokohama, 230-8501, Japan.
J Physiol Sci. 2023 Aug 9;73(1):18. doi: 10.1186/s12576-023-00873-5.
In this work, we examined the involvement of type 5 adenylyl cyclase (AC5) in cardiac dysfunction induced in mice given Porphyromonas gingivalis lipopolysaccharide (PG-LPS) at a dose equivalent to the circulating levels in periodontitis (PD) patients. Cardiac function was significantly decreased in mice given PG-LPS compared to the control, but treatment for 1 week with the AC5 inhibitor vidarabine ameliorated the dysfunction. Cardiac fibrosis and myocyte apoptosis were significantly increased in the PG-LPS group, but vidarabine blocked these changes. The PG-LPS-induced cardiac dysfunction was associated with activation of cyclic AMP/Ca-calmodulin-dependent protein kinase II signaling and increased phospholamban phosphorylation at threonine 17. These results suggest that pharmacological AC5 inhibition may be a promising approach to treat PD-associated cardiovascular disease.
在这项工作中，我们研究了 5 型腺苷酸环化酶（AC5）在牙周炎（PD）患者循环水平相当剂量的牙龈卟啉单胞菌脂多糖（PG-LPS）诱导的小鼠心脏功能障碍中的作用。与对照组相比，给予 PG-LPS 的小鼠心脏功能明显下降，但用 AC5 抑制剂阿昔洛韦治疗 1 周可改善心脏功能障碍。PG-LPS 组的心肌纤维化和心肌细胞凋亡明显增加，但阿昔洛韦阻断了这些变化。PG-LPS 诱导的心脏功能障碍与环磷酸腺苷/钙调蛋白依赖性蛋白激酶 II 信号的激活以及 Thr17 磷酸化增加有关。这些结果表明，药理学抑制 AC5 可能是治疗 PD 相关心血管疾病的一种有前途的方法。
