Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Figures

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  Figure 1. Food items rich in arachidonic acid. Chicken and chicken-mixed dishes, eggs, beef and beef products, pork and pork products, invertebrates and fish, breast milk and infant formula milk powder provide the most arachidonic acid intake to humans. Prostaglandin (PG)D2, PGE2, PGF2α, prostacyclin (PGI2), and thromboxanes (TX)A2 are major arachidonic acid metabolites. These polyunsaturated fatty acids play an important role in their growth and reproduction.

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  Figure 2. Arachidonic acid metabolism. Arachidonic acid is released from phospholipid by phospholipase A2 (PLA2) and, in turn, is metabolized through three different pathways involving cyclooxygenase (COX), cytochrome P450 (CYP) enzymes, or lipoxygenase (LOX). COX-1 and COX-2 convert arachidonic acid to prostaglandin (PG)G2 and PGH2, which are further metabolized to various prostaglandins (PGs) such as PGD2, PGE2, PGF2α, prostacyclin (PGI2), and thromboxanes (TX)A2 by corresponding synthases, i.e., PGD2 synthase (PGDS), PGE2 synthase (PGES), PGF2α synthase (PGFS), PGI2 synthase (PGIS), and TXA2 synthase (TXAS). LOXs catalyze the dioxygenation of polyunsaturated fatty acids to their corresponding hydroperoxyeicosatetraenoic acids (HPETEs), which are subsequently converted to hydroxyeicosatetraenoic acids (HETEs), leukotrienes (LTs), and lipoxins (LXs). CYP generates HETEs and epoxyeicosatrienoic acids (EETs).

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  Figure 3. Regulation of vascular tone by arachidonic acid metabolites. Arachidonic acid metabolites produced in endothelial cell (EC) including prostaglandin (PG)D2, PGE2, PGF2α, prostacyclin (PGI2), and thromboxanes (TX)A2 target to their corresponding receptor in smooth muscle cell (SMC), increasing intracellular cAMP level [cAMP]i to induce relaxation or decreasing intracellular calcium level [Ca2+]i to induce contraction.

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  Figure 4. Effects of arachidonic acid metabolites on cardiovascular diseases. Various metabolites including prostaglandin (PG)D2 and PGE2 (to EP1, EP2, EP3 or EP4 receptor), prostacyclin (PGI2), thromboxane (TX)A2, leukotrienes B4 (LTB4) (to CysLT receptors), lipoxin A4 (LXA4), hydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs) exert vasoprotective (labeled with blue color) and deteriorative effects (labeled with red color).