Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice

Abstract 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 decr...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Journal of Physiological Sciences
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Online Access:https://doi.org/10.1186/s12576-023-00873-5
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Summary:Abstract 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.
ISSN:1880-6562