School of Medical Sciences, Royal Melbourne Institute of Technology University, Bundoora, Victoria, Australia.
Am J Physiol Heart Circ Physiol. 2010 Jan;298(1):H171-8. doi: 10.1152/ajpheart.00699.2009. Epub 2009 Oct 23.
Hyperglycemia is a major risk factor for endothelial dysfunction and vascular disease, and in the current study, the link to glucose-induced abnormal intracellular Ca(2+) (Ca(i)(2+)) homeostasis was explored in bovine aortic endothelial cells in high glucose (HG; 25 mmol/l) versus low glucose (LG; 5.5 mmol/l; control). Transient receptor potential 1 (TRPC1) ion channel protein, but not TRPC3, TRPC4, or TRPC6 expression, was significantly increased in HG versus LG at 72 h. HG for 4, 24, and 72 h did not change basal Ca(i)(2+) or ATP-induced Ca(i)(2+) release; however, the amplitude of sustained Ca(i)(2+) was significantly increased at 24 and 72 h and reduced by low concentration of the putative, but nonspecific, TRPC blockers, gadolinium, SKF-96365, and 2-aminoethoxydiphenyl borate. Treatment with TRPC1 antisense significantly reduced TRPC1 protein expression and ATP-induced Ca(2+) entry in bovine aortic endothelial cells. Although the link between HG-induced changes in TRPC1 expression, enhanced Ca(2+) entry, and endothelial dysfunction require further study, the current data are suggestive that targeting these pathways may reduce the impact of HG on endothelial function.
高血糖是内皮功能障碍和血管疾病的一个主要危险因素，在本研究中，我们探讨了在高葡萄糖（HG；25mmol/L）与低葡萄糖（LG；5.5mmol/L；对照）环境中，牛主动脉内皮细胞中葡萄糖诱导的异常细胞内 Ca(2+)（Ca(i)(2+)）稳态与葡萄糖诱导的异常细胞内 Ca(2+)（Ca(i)(2+)）稳态之间的联系。瞬时受体电位 1（TRPC1）离子通道蛋白，但不是 TRPC3、TRPC4 或 TRPC6 表达，在 HG 中与 LG 相比在 72 小时时显著增加。HG 孵育 4、24 和 72 小时并不改变基础 Ca(i)(2+)或 ATP 诱导的 Ca(i)(2+)释放；然而，在 24 和 72 小时时，持续的 Ca(i)(2+)幅度显著增加，而低浓度的假定但非特异性的 TRPC 阻滞剂钆、SKF-96365 和 2-氨基乙氧基二苯硼酸盐可减少其幅度。TRPC1 反义处理显著降低了牛主动脉内皮细胞中 TRPC1 蛋白表达和 ATP 诱导的 Ca(2+)内流。虽然 HG 诱导的 TRPC1 表达变化、增强的 Ca(2+)内流与内皮功能障碍之间的联系需要进一步研究，但目前的数据表明，靶向这些途径可能会降低 HG 对内皮功能的影响。
