Alterations of Arachidonate Metabolism in Cardiovascular System by Cigarette Smoking
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Cigarette smoking is known to be a major risk factor for the development of a variety of cardiovascular diseases including myocardial infarction, thromboembolism and atherosclerosis(l). The underlying mechanisms by which cigarette smoking can contribute to these disorders are yet to be defined. Recently, two families of biologically potent fatty acids were discovered and found to have profound effects on the cardiopulmonary system(2,3). They may play dominant roles in the physiology of vascular homeostasis and in the pathophysiology of thrombosis, atherosclerosis and emphysema. Both families of fatty acids are derived from arachidonic acid by two separate pathways. The cyclooxygenase pathway leads to the formation of intermediary prostaglandin endoperoxides (PGG2, PGH2) followed by the synthesis of vasoconstrictive and proaggregatory thromboxane A2(TXA2) in platelets(4) and that of vasodilatory and anti-aggregatory prostacyclin (PGI2) in vascular wall(5). The opposing action of TXA2 and PGI2 provides a balanced interaction between platelets and vascular cells. TXA2, PGI2 and other prostaglandins (PG) are oxidized and inactivated by NAD+ -dependent 15-hydroxy prostaglandin dehydrogenase present in various tissues(6,7). The lipoxygenase pathway involves the formation of chemotactic 12-hydroxyeicosa-tetraenoic acid (12-HETE) in platelets(8) and possibly in vascular cells(9). This hydroxy fatty acid may control the migration and proliferation of smooth muscle cells in the development of atherosclerotic plaques(10).
KeywordsArachidonic Acid Cigarette Smoke Smoke Exposure Cigarette Smoke Exposure Lipoxygenase Pathway
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