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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author 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
author_facet 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
author_sort Michinori Tsunoda
collection DOAJ
description 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.
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spelling doaj-art-60baea73f6df4ecd83da5facbcedeffb2025-08-20T02:35:18ZengElsevierJournal of Physiological Sciences1880-65622023-08-0173111210.1186/s12576-023-00873-5Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in miceMichinori Tsunoda0Ichiro Matsuo1Yoshiki Ohnuki2Kenji Suita3Misao Ishikawa4Takao Mitsubayashi5Aiko Ito6Yasumasa Mototani7Kenichi Kiyomoto8Akinaka Morii9Megumi Nariyama10Yoshio Hayakawa11Kazuhiro Gomi12Satoshi Okumura13Department of Physiology, Tsurumi University School of Dental MedicineDepartment of Periodontology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Oral Anatomy, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Orthodontology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineDepartment of Pediatric Dentistry, Tsurumi University School of Dental MedicineDepartment of Dental Anesthesiology, Tsurumi University School of Dental MedicineDepartment of Periodontology, Tsurumi University School of Dental MedicineDepartment of Physiology, Tsurumi University School of Dental MedicineAbstract 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.https://doi.org/10.1186/s12576-023-00873-5β-Adrenergic signalingPeriodontitisAdenylyl cyclaseApoptosisFibrosisSignal transduction
spellingShingle 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
Journal of Physiological Sciences
β-Adrenergic signaling
Periodontitis
Adenylyl cyclase
Apoptosis
Fibrosis
Signal transduction
title Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice
title_full Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice
title_fullStr Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice
title_full_unstemmed Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice
title_short Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice
title_sort vidarabine an anti herpes agent improves porphyromonas gingivalis lipopolysaccharide induced cardiac dysfunction in mice
topic β-Adrenergic signaling
Periodontitis
Adenylyl cyclase
Apoptosis
Fibrosis
Signal transduction
url https://doi.org/10.1186/s12576-023-00873-5
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