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 and Dimmeler, S, 2001. Vitamin C inhibits endothelial cell apoptosis in congestive heart failure. Circulation, 104 (18), pp. 2182-2187. ISSN 0009-7322

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Abstract

Background - Proinflammatory cytokines like tumor necrosis factor- 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- 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.

Item Type:	Journal article
Publication Title:	Circulation
Creators:	Rossig, L., Hoffmann, J., Hugel, B., Mallat, Z., Haase, A., Freyssinet, J.M., Tedgui, A., Aicher, A., Zeiher, A.M. and Dimmeler, S.
Publisher:	American Heart Association
Date:	2001
Volume:	104
Number:	18
ISSN:	0009-7322
Identifiers:	Number Type 10.1161/hc4301.098284 DOI
Divisions:	Schools > School of Science and Technology
Record created by:	EPrints Services
Date Added:	09 Oct 2015 11:07
Last Modified:	23 Aug 2016 09:13
URI:	https://irep.ntu.ac.uk/id/eprint/23132

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