Submitted on July 27, 2009
Revised on October 7, 2009
Accepted on October 15, 2009
Glucose enhances expression of TRPC1 and Ca entry in endothelial cells
Nour B. Bishara1 and Hong Ding2*
1 RMIT
2 WCMC-Q
* To whom correspondence should be addressed. E-mail: hod2005{at}qatar-med.cornell.edu.
Hyperglycemia is a major risk factor for endothelial dysfunction and vascular disease and, in the current study, the link to glucose-induced abnormal intracellular calcium (Ca2+i) homeostasis was explored in bovine aortic endothelial cells (BAECs) in high glucose (HG) (25 mmol/L) versus control (low glucose, LG) (5.5 mmol/L). Transient receptor potential 1 (TRPC1) ion channel protein, but not TRPC3, TRPC4 or TRPC6 expression, was significantly increased in HG vs. LG at 72 h. HG for 4, 24 and 72 h did not change basal Ca2+i or ATP-induced Ca2+i release, however, the amplitude of sustained Ca2+i was significantly increased at 24 and 72 h and reduced by low concentration of the putative, but non-specific, TRPC blockers, gadolinium (Gd3+), SKF96365 and 2-aminoethoxydiphenyl borate (2-APB). Treatment with TRPC1 antisense significantly reduced TRPC1 protein expression and ATP-induced Ca2+ entry in BAECs. Although the link between HG-induced changes in TRPC1 expression, enhanced Ca2+ entry and endothelial dysfunction requires further study, the current data are suggestive that targeting these pathways may reduce the impact of HG on endothelial function.
