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 indicing several protein kinases such as protein kinase C, tyrosine kinase and mitogen activated protein kinases. Oxindant-mediated alteration of different signal transduction systems and their interations eventually regulate a variety of pathological conditoins such as atherosclerosis, apoptosis and necrosis in the myocardium