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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Elsevier
2023-08-01
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| 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. |
| format | Article |
| id | doaj-art-60baea73f6df4ecd83da5facbcedeffb |
| institution | OA Journals |
| issn | 1880-6562 |
| language | English |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Physiological Sciences |
| 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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