부산대학교 도서관

Background PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone. Methods A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca.sup.2+ ].sub.i , a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells). Results PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K.sup.+ -induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K.sup.+ channel blockers (Gli/TEA). PFI-3 abolished Ca.sup.2+ -induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca.sup.2+ -free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca.sup.2+ -induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60mM) in Ca.sup.2+ -free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques. Conclusions PFI-3 blunted PE and high K.sup.+ -induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).
Author(s): Jing Li (1), Xue-Qi Liang (2), Yun-Feng Cui (1), Yu-Yang Fu (1), Zi-Yue Ma (1), Ying-Tao Cui (1), Xian-Hui Dong (1), Hai-Jun Huang (1), Ting-Ting Tong (1), Ya-Mei Zhu [...]