Lipoxin A4 promotes autophagy and inhibits overactivation of macrophage inflammasome activity induced by Pg LPS.

OBJECTIVE: To explore the role of lipoxin A4 (LXA4) on inflammasome and inflammatory activity in macrophages activated by Porphyromonas gingivalis lipopolysaccharide (PgLPS) one of the major causative agents of chronic periodontitis. METHODS: The mouse macrophage cell line RAW264.7 was used to produce an activated inflammation model. Markers of inflammasome and inflammatory activity and autophagy were assessed by ELISA, reverse transcription polymerase chain reaction (RT-PCR), and Western blot assay. RESULTS: Markers of inflammasome activity, inflammation and autophagy increased with Pg LPS concentration. They also increased with increasing exposure to Pg LPS up to 12h but decreased at 24h. However, markers of autophagy increased. Phosphorylated NF-κBp65 decreased with LXA4, which was similar to results obtained with the autophagy inducer, rapamycin. CONCLUSIONS: LXA4 promoted autophagy and inhibited activation of inflammasomes and inflammation markers in macrophage inflammation induced by PgLPS and this action was linked to the phosphorylation of NF-κB.

Nicorandil reversed homocysteine-induced coronary microvascular dysfunction via regulating PI3K/Akt/eNOS pathway.

OBJECTIVE: Nicorandil exerts a protective effect against coronary microvascular dysfunction in acute myocardial infarction (AMI) patients. However, the mechanism and effect of nicorandil in hyperhomocysteinemia (HHcy) AMI patients remain unclear. METHODS: C57/BL6 mice with mild to moderate HHcy and human coronary artery endothelial cells (HCAECs) cotreated with HHcy (1 mmol/L) for 24 h and hypoxia for 6 h were selected as models. Small animal ultrasound detection was used to compare cardiac function. CD31 immunofluorescence staining and tomato lectin staining were used to assess the number of microcirculation changes in vivo. MTT, tube formation and western blotting assays were used to evaluate the effect of nicorandil on HCAECs and the PI3K/Akt/eNOS pathway. RESULTS: The results showed that nicorandil improved cell viability and p-PI3K/PI3K, p-Akt/Akt, and p-eNOS/eNOS expression in the vitro HHcy and hypoxia models. The beneficial effects of nicorandil on HCAECs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the nitric oxide synthase (NOS) inhibitor L-NAME. In vivo, nicorandil improved the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the post-HHcy + MI model, and the levels of CD31 and tomato lectin expression were higher in the nicorandil treatment group. The effectiveness of nicorandil was inhibited in the PI3K and L-NAME groups. CONCLUSION: The results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway.