Poster session

[P2-3-30] Role of cardiac adenylyl cyclase for the development of Porphyromonas gngivalis LPS-induced cardiac dysfunction

〇Michinori Tsunoda¹, Yoshiki Ohnuki², Kenji Suita², Ichiro Matsuo¹, Yoshio Hayakawa³, Kenichi Kiyomoto¹, Akinaka Morii¹, Megumi Nariyama⁴, Kazuhiro Gomi¹, Satoshi Okumura² (1. Dept Periodont, Tsurumi Univ Sch Dent Med , 2. Dept Physiol, Tsurumi Univ Sch Dent Med, 3. Dept Anesthesiol, Tsurumi Univ Sch Dent Med, 4. Dept Pediatr Dent, Tsurumi Univ Sch Dent Med)

Keywords:PG-LPS、抗ウィルス薬ビダラビン、AC5

Cardiovascular disease (CVD) is a major cause of physical frailty and mortality, and chronic stimulation of the sympathetic nervous system is a common cause of CVD in patients. There are nine major mammalian isoforms of adenylyl cyclase (AC), with type 5 AC (AC5) being the major cardiac isoform in adults. In this work, we examined the involvement of type 5 adenylyl cyclase (AC5) in cardiac dysfunction induced in mice given Porphrlomonas gingivalis lipopolysaccharide (PG-LPS) at a dose equivalent to the circulating levels in patients of periodontitis (PD). Mice were divided into 4 groups: 1) Control, 2) PG-LPS (0.8mg/kg/day: ip), 3)Vid (15mg/kg/day: osmotic pump) and 4) Vid+PG-LPS. 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.