Vitamin C inhibits endothelial cell apoptosis in congestive heart failure

Background-Proinflammatory cytokines like tumor necrosis factor-alpha and o xidative stress induce apoptotic cell death in endothelial cells (ECs). Sys temic inflammation and increased oxidative stress in congestive heart failu re (CHF) coincide with enhanced EC apoptosis and the development of endothe lial dysfunction. Therefore, we investigated the effects of antioxidative v itamin C therapy on EC apoptosis in CHF patients. Methods and Results-Vitamin C dose dependently suppressed the induction of EC apoptosis by tumor necrosis factor-a and angiotensin II in vitro as asse ssed by DNA fragmentation, DAPI nuclear staining, and MTT viability assay. The antiapoptotic effect of vitamin C was associated with reduced cytochrom e C release from mitochondria and the inhibition of caspase-9 activity. To assess EC protection by vitamin C in CHF patients, we prospectively randomi zed CHF patients in a double-blind trial to vitamin C treatment versus plac ebo. Vitamin C administration to CHF patients markedly reduced plasma level s of circulating apoptotic microparticles to 32 +/-8% of baseline levels, w hereas placebo had no effect (87 +/- 14%, P <0.005). In addition, vitamin C administration suppressed the proapoptotic activity on EC of the serum of CHF patients (P <0.001). Conclusions-Administration of vitamin C to CHF patients suppresses EC apopt osis in vivo, which might contribute to the established functional benefit of vitamin C supplementation on endothelial function.