Vitamin C insufficiency causes the stress-induced sudden death through the induction of extensive heart injury.

Abstract

Vitamin C scavenges toxic free radicals as an antioxidant, and oxidative stress is considered as a major contributor inducing damage to cardiomyocytes in heart diseases. Also, it is well-known that stress provokes oxidative stress and induces cardiac sudden death. Here we show the effects of vitamin C on the prevention of cardiac damage by stress in gulo(-/-) mice which cannot synthesize vitamin C. Vitamin C-insufficient gulo(-/-) mice under stress showed prominent cardiac damage and expired within 2 weeks. It was accompanied with structural changes in the heart, cardiac dysfunction and severe emphysema. These changes were caused by the elevation of pro-inflammatory cytokines, especially TNF-&x03B1;, the activation of MMP-2/MMP-9, an increase in oxidative stress and a remarkable decrease in noradrenaline production. Thus, vitamin C insufficiency causes extensive cardiac damage under stress through regulating cytokine and hormone production as well as redox homeostasis, which results in stress-induced sudden death.