Nicorandil inhibits serum starvation-induced apoptosis in vascular endothelial cells

Area of Science:

• Cardiovascular Pharmacology
• Cell Biology
• Endothelial Function

Background:

• The Impact Of Nicorandil in Angina (IONA) trial demonstrated nicorandil's efficacy in reducing coronary events in stable angina patients.
• The specific impact of nicorandil on endothelial cell apoptosis has not been fully elucidated.

Purpose of the Study:

• To investigate the hypothesis that nicorandil exerts anti-apoptotic effects on endothelial cells (ECs).
• To explore the underlying mechanisms of nicorandil's potential protective actions on endothelial cells.

Main Methods:

• Human umbilical vein endothelial cells (ECs) were subjected to serum starvation to induce apoptosis.
• The effects of nicorandil on cell viability and apoptosis markers (caspase 3 activation, Hoechst 33258 assay) were assessed.
• The role of mitochondrial KATP channels was examined using a specific blocker (5-Hydroxydecanoic acid) and a mitochondrial permeability transition pore activator.

Main Results:

• Nicorandil significantly increased endothelial cell viability under serum starvation conditions (81% vs. 63%).
• Nicorandil effectively abrogated serum starvation-induced apoptosis, as evidenced by reduced caspase 3 activation and Hoechst 33258 staining.
• The anti-apoptotic effects were inhibited by a mitochondrial KATP channel blocker and a mitochondrial permeability transition pore activator, implicating mitochondrial pathways.

Conclusions:

• Nicorandil demonstrates significant anti-apoptotic effects in endothelial cells subjected to serum starvation.
• The protective mechanism of nicorandil appears to involve the modulation of mitochondrial apoptotic pathways via mitochondrial KATP channels.
• These findings suggest a potential role for nicorandil in preserving endothelial integrity beyond its known anti-anginal effects.