Nitric Oxide And Apoptosis

Cardiac myocytes undergo apoptosis in humans with dilated cardiomyopathies.127,128 Cardiac myocyte apoptosis may also occur in humans with myocarditis. Because cox-sackievirus can cause apoptosis in cardiac myocytes, directly triggering apoptosis and indirectly activating cytotoxic T lymphocytes, patients with viral myocarditis probably lose cardiac myocytes by apoptosis. Thus, apoptosis may be a prominent feature of infectious myocarditis.

NO may protect the heart by inhibiting apoptosis via different mechanisms. First, NO directly inhibits replication of pathogens such as the coxsackievirus that causes apop-tosis. A lower viral burden means that fewer viral antigens are presented to cytotoxic T lymphocytes that kill infected cells through apoptosis. Second, NO can inhibit pathogen enzymes that trigger apoptosis. For example, NO inhibits the coxsackievirus 3C protease that cleaves BID and triggers the mitochondrial apoptosis pathway (unpublished data). Third, NO can inhibit caspases that are part of the intracellular apoptotic cascade. Caspases are cysteine proteases, and NO can nitrosylate cysteine residues, inactivating enzymes such as caspases that contain cysteine at their active site. Several groups have shown that NO can nitrosylate caspase-3, inhibit caspase activity, and inhibit apoptosis.129-132 Thus, NO may protect the heart and preserve cardiac myocytes by inhibiting cardiac cell death.

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