Targets of oxidative stress in cardiovascular system.

Although oxidants such as superoxide (O2.) and hydrogen peroxide (H2O2) play a role in host-mediated destruction of foreign pathogens yet excessive generation of oxidants may lead to a variety of pathological complications in the cardiovascular system. An important mechanism by which oxidants cause dysfunction of the cardiovascular system appears to be due to the increase in intracellular free Ca2+ concentration. Oxidants cause cellular Ca2+ mobilization by modulating activities of a variety of regulators such as Na+/H+ and Na+/Ca2+ exchangers, Na+/K+ ATPase and Ca2+ ATPase and Ca2+ channels that are associated with Ca2+ transport in the plasma membrane and the sarco(endo)plasmic reticular membrane of myocardial cells. Recent research have suggested that the increase in Ca2+ level by oxidants plays a pivotal role in inducing several protein kinases such as protein kinase C, tyrosine kinase and mitogen activated protein kinases. Oxidant-mediated alteration of different signal transduction systems and their interations eventually regulate a variety of pathological conditions such as atherosclerosis, apoptosis and necrosis in the myocardium.