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(Circulation Research. 2004;95:443.)
© 2004 American Heart Association, Inc.

Editorials

Beating Ischemia

A New Feat of EETs?

Aruni Bhatnagar

From the Institute of Molecular Cardiology, University of Louisville, Louisville, Ky.

Correspondence to Aruni Bhatnagar, PhD, Division of Cardiology, Department of Medicine, Delia Baxter Bldg, 580 S Preston St, Room 421F, University of Louisville, Louisville, KY 40202. E-mail aruni@louisville.edu

See related article, pages 506–514

Key Words: cytochrome P450 • myocardial ischemia • epoxyeicosatrienoic acid (EET) • mitochondria • ATP-dependent K⁺ channel

An extract of the first 250 words of the full text is provided, because this article has no abstract.

It is well-known that myocardial ischemia results in the hydrolysis of phospholipids and the generation of arachidonic acid. Free arachidonic acid also could accumulate as a result of hormonal activation or the failure of fatty acid oxidation in the ischemic heart. What happens next to arachidonic acid and how its many metabolites (see the Figure) affect myocardial function is not entirely clear, but questions related to these issues are turning out some of the most fascinating and provocative answers in cardiovascular physiology. Much of the current evidence, however, is conflicting. Increased arachidonic acid metabolism via cyclooxygenases mediates the cardioprotective effects of the late phase of ischemic preconditioning¹ and provides long-term protection to the heart against ischemic injury.² However, treatment with cytochrome P450 (CYP) inhibitors³ or inhibition of mitochondrial calcium-independent phospholipase A₂ (which liberates arachidonic acid from phospholipid stores) reduces infarct size,⁴ suggesting that increased generation of arachidonic acid and its metabolites could be detrimental to the ischemic heart. Adding new fuel to this debate is the elegant study by Seubert et al,⁵ published in the current issue of Circulation Research, which shows that increased CYP-dependent epoxidation of arachidonic acid to cis-epoxyeicosatrienoic acids (EETs) could decrease myocardial ischemic injury. Using transgenic mice overexpressing human CYP2J2 in the heart, these investigators demonstrate improved postischemic recovery of the heart and suggest that this protection is attributable to the activation of the mitochondrial K_ATP channel (mitoK_ATP) and the stimulation of the p42/p44 MAP kinase pathway. Their convincing demonstration of a . . . [Full Text of this Article]

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