Compounds > inositol-1-4-5-trisphosphate

inositol-1-4-5-trisphosphate and Pulmonary-Arterial-Hypertension

inositol-1-4-5-trisphosphate has been researched along with Pulmonary-Arterial-Hypertension* in 1 studies

Other Studies

1 other study(ies) available for inositol-1-4-5-trisphosphate and Pulmonary-Arterial-Hypertension

Article	Year
Melatonin inhibits inflammasome-associated activation of endothelium and macrophages attenuating pulmonary arterial hypertension. Cardiovascular research, 2020, 11-01, Volume: 116, Issue:13 Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome associated with pulmonary/systemic inflammation. Melatonin relieves PAH, but the molecular mode of action remains unclear. Here, we investigated the role of melatonin in normalizing vascular homeostasis.. Light-time mean serum melatonin concentration was lower in patients with PAH than in normal controls [11.06 ± 3.44 (7.13-15.6) vs. 14.55 ± 1.28 (8.0-19.4) pg/mL], which was negatively correlated with increased serum levels of interleukin-1β (IL-1β) in patients with PAH. We showed that inflammasomes were activated in the PAH mice model and that melatonin attenuated IL-1β secretion. On one hand, melatonin reduced the number of macrophages in lung by inhibiting the endothelial chemokines and adhesion factors. Moreover, use of Il1r-/- mice, Caspase1/11-/- mice, and melatonin-treated mice revealed that melatonin reduced hypoxia-induced vascular endothelial leakage in the lung. On the other hand, we verified that melatonin reduced the formation of inflammasome multiprotein complexes by modulating calcium ions in macrophages using a live cell station, and melatonin decreased inositol triphosphate and increased cAMP. Furthermore, knockdown of melatonin membrane receptors blocked melatonin function, and a melatonin membrane receptors agonist inactivated inflammasomes in macrophages.. Melatonin attenuated inflammasome-associated vascular disorders by directly improving endothelial leakage and decreasing the formation of inflammasome multiprotein complexes in macrophages. Taken together, our data provide a theoretical basis for applying melatonin clinically, and inflammasomes may be a possible target of PAH treatment. Topics: Adult; Animals; Anti-Inflammatory Agents; Biomarkers; Calcium; Case-Control Studies; Caspase 1; Caspases, Initiator; Cells, Cultured; Cyclic AMP; Disease Models, Animal; Endothelial Cells; Female; Human Umbilical Vein Endothelial Cells; Humans; Inflammasomes; Inositol 1,4,5-Trisphosphate; Interleukin-1beta; Macrophage Activation; Macrophages, Peritoneal; Male; Melatonin; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Permeability; Pulmonary Arterial Hypertension; Receptors, Interleukin-1 Type I; Receptors, Melatonin; Signal Transduction	2020

Article

Year

Melatonin inhibits inflammasome-associated activation of endothelium and macrophages attenuating pulmonary arterial hypertension.

Cardiovascular research, 2020, 11-01, Volume: 116, Issue:13

Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome associated with pulmonary/systemic inflammation. Melatonin relieves PAH, but the molecular mode of action remains unclear. Here, we investigated the role of melatonin in normalizing vascular homeostasis.. Light-time mean serum melatonin concentration was lower in patients with PAH than in normal controls [11.06 ± 3.44 (7.13-15.6) vs. 14.55 ± 1.28 (8.0-19.4) pg/mL], which was negatively correlated with increased serum levels of interleukin-1β (IL-1β) in patients with PAH. We showed that inflammasomes were activated in the PAH mice model and that melatonin attenuated IL-1β secretion. On one hand, melatonin reduced the number of macrophages in lung by inhibiting the endothelial chemokines and adhesion factors. Moreover, use of Il1r-/- mice, Caspase1/11-/- mice, and melatonin-treated mice revealed that melatonin reduced hypoxia-induced vascular endothelial leakage in the lung. On the other hand, we verified that melatonin reduced the formation of inflammasome multiprotein complexes by modulating calcium ions in macrophages using a live cell station, and melatonin decreased inositol triphosphate and increased cAMP. Furthermore, knockdown of melatonin membrane receptors blocked melatonin function, and a melatonin membrane receptors agonist inactivated inflammasomes in macrophages.. Melatonin attenuated inflammasome-associated vascular disorders by directly improving endothelial leakage and decreasing the formation of inflammasome multiprotein complexes in macrophages. Taken together, our data provide a theoretical basis for applying melatonin clinically, and inflammasomes may be a possible target of PAH treatment.

Topics: Adult; Animals; Anti-Inflammatory Agents; Biomarkers; Calcium; Case-Control Studies; Caspase 1; Caspases, Initiator; Cells, Cultured; Cyclic AMP; Disease Models, Animal; Endothelial Cells; Female; Human Umbilical Vein Endothelial Cells; Humans; Inflammasomes; Inositol 1,4,5-Trisphosphate; Interleukin-1beta; Macrophage Activation; Macrophages, Peritoneal; Male; Melatonin; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Permeability; Pulmonary Arterial Hypertension; Receptors, Interleukin-1 Type I; Receptors, Melatonin; Signal Transduction

2020