An integrated proposal to explain the epidemic of cardiovascular disease in a developing country

An increase of coronary artery disease has been observed in developing countries during the last years. Various factors may explain this accelerated increase. We propose that inappropriate diet and inadequate sanitary infrastructure may act as triggers to create an imbalance between nitric oxide (NO) and superoxide (O₂ ^-). An increase in the concentrations of oxidized LDL produces both decreased NO and increased O₂ ^-endothelial synthesis, by accumulation of asymmetrical N^G-N^G-dimethyl-L-arginine, the endogenous inhibitor of NO, and by activation of NAD(P)H oxidase. On the other hand, high rates of chronic infection-inflammation, due to inappropriate sanitary environment stimulate higher circulating levels of proinflammatory cytokines. These cytokines also contribute to reduced NO and increased O₂ ^- endothelial production through the same mechanisms of oxidized LDL. The net result of this imbalance is an increased generation of peroxynitrate that injures the endothelium in a proatherogenic, prothrombotic and vasoconstrictive manner.