Li, Linyi published the artcileSalidroside ameliorated intermittent hypoxia-aggravated endothelial barrier disruption and atherosclerosis via the cAMP/PKA/RhoA signaling pathway, Application of 2′,7′-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate, the main research area is salidroside cAMP PKA RhoA endothelial barrier disruption atherosclerosis pathway; atherosclerosis; endothelial barrier; intermittent hypoxia; obstructive sleep apnea-hypopnea syndrome; salidroside.
Endothelial barrier dysfunction plays a key role in atherosclerosis progression. The primary pathol. of obstructive sleep apnea-hypopnea syndrome is chronic intermittent hypoxia (IH), which induces reactive oxygen species (ROS) overproduction, endothelial barrier injury, and atherosclerosis. Salidroside, a typical pharmacol. constituent of Rhodiola genus, has documented antioxidative, and cardiovascular protective effects. However, whether salidroside can improve IH-aggravated endothelial barrier dysfunction and atherosclerosis has not been elucidated. In normal chow diet-fed ApoE-/- mice, salidroside (100 mg/kg/d, p. o.) significantly ameliorated the formation of atherosclerotic lesions and barrier injury aggravated by 7-wk IH (21%-5%-21%, 120 s/cycle). In human umbilical vein endothelial cells (HUVECs), exposure to IH (21%-5%-21%, 40 min/cycle, 72 cycles) decreased transendothelial elec. resistance and protein expression of vascular endothelial cadherin (VE-cadherin) and zonula occludens 1. In addition, IH promoted ROS production and activated ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway. All of these effects of IH were reversed by salidroside. Similar to salidroside, ROCK-selective inhibitors Y26732, and Fasudil protected HUVECs from IH-induced ROS overproduction and endothelial barrier disruption. Furthermore, salidroside increased intracellular cAMP levels, while the PKA-selective inhibitor H-89 attenuated the effects of salidroside on IH-induced RhoA/ROCK suppression, ROS scavenging, and barrier protection. Our findings demonstrate that salidroside effectively ameliorated IH-aggravated endothelial barrier injury and atherosclerosis, largely through the cAMP/PKA/RhoA signaling pathway.
Frontiers in Pharmacology published new progress about Apolipoprotein E Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 2044-85-1 belongs to class esters-buliding-blocks, name is 2′,7′-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate, and the molecular formula is C24H14Cl2O7, Application of 2′,7′-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate.
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