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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/Ca2+-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. © 2023. The Physiological Society of Japan.


Michinori Tsunoda, Ichiro Matsuo, Yoshiki Ohnuki, Kenji Suita, Misao Ishikawa, Takao Mitsubayashi, Aiko Ito, Yasumasa Mototani, Kenichi Kiyomoto, Akinaka Morii, Megumi Nariyama, Yoshio Hayakawa, Kazuhiro Gomi, Satoshi Okumura. Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice. The journal of physiological sciences : JPS. 2023 Aug 09;73(1):18

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PMID: 37558983

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