Calcium channel blocker (diltiazem) inhibits apoptosis of vascular smooth muscle cell exposed to high glucose concentration through lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) pathway.

AIM to examine the role of diltiazem in the prevention of VSMC apoptosis exposed to high glucose through inhibition of LOX-1 expression. METHODS we performed experimental study on the primary culture of VSMCs. Expression LOX-1, and Caspase-3 activity (a key regulatory protease at which many signaling pathways merge for the execution of apoptosis) were measured by Elisa. Data were expressed as mean ± SEM. The statistical significance was assessed by one-way analysis of variance (ANOVA) followed by post hock analysis by Turckey test, p<0.05 was considered statistically significant. RESULTS chronic exposed VSMC to high glucose concentration (25 mM), increase cytosolic Ca++ concentration (3127 ± 413.89 v.s. 2011.81 ± 410.93 unit/cell, p<0.01), expression of LOX-1 ((506.80 ± 10.47 v.s. 458.40 ± 36.49 ng/ml, p<0.05), and caspase-3 activity (129.98 ± 5.97 v.s. 114.73 ± 10.84%, p<0.05) respectively, compare exposed to 5mM glucose concentration. LOX-1 was related to caspase-3 activity, pre-treated with inhibitor LOX-1 activity, k-carragenan before being exposed to glucose 25 mM, prevents the increasing of caspase-3 activity (96.41 ± 5.11 v.s. 129.98 ± 5.98 %, p<0.01). Pre incubation with 10μM of diltiazem before being exposed to 25 mM glucose concentration significantly inhibits the elevation of cytosolic Ca++ concentration (2149.61 ± 339.49 v.s. 3127 ± 413.89 unit/cell, p<0.01), LOX-1 expression (468,60 ± 14.44 v.s. 506.80 ± 10.47 ng/ml, p < 0.05), and caspase-3 activity (82.50 ± 9.90 v.s. 129.98 ± 5.97%, p<0.01). CONCLUSION overall, these results demonstrate that high glucose induces VSMCs apoptosis through caspase-3 pathway. This effect appears to be inhibited by diltiazem through decreasing LOX-1 expression and activity.