Heart Failure
Vitamin C inhibits endothelial cell apoptosis in congestive heart failure.
Rossig L; Hoffmann J; Hugel B; Mallat Z; Haase A; Freyssinet
JM; Tedgui A; Aicher A; Zeiher AM; Dimmeler S
Circulation 2001 Oct 30;104(18):2182-7
BACKGROUND: Proinflammatory cytokines like tumor necrosis factor-alpha
and oxidative stress induce apoptotic cell death in endothelial cells
(ECs). Systemic inflammation and increased oxidative stress in congestive
heart failure (CHF) coincide with enhanced EC apoptosis and the development
of endothelial dysfunction. Therefore, we investigated the effects of
antioxidative vitamin 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-alpha and angiotensin II in vitro as
assessed by DNA fragmentation, DAPI nuclear staining, and MTT viability
assay. The antiapoptotic effect of vitamin C was associated with reduced
cytochrome C release from mitochondria and the inhibition of caspase-9
activity. To assess EC protection by vitamin C in CHF patients, we prospectively
randomized CHF patients in a double-blind trial to vitamin C treatment
versus placebo. Vitamin C administration to CHF patients markedly reduced
plasma levels of circulating apoptotic microparticles to 32+/-8% of baseline
levels, whereas 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 apoptosis in vivo, which might
contribute to the established functional benefit of vitamin C supplementation
on endothelial function. |
