Unraveling the Role of 12- and 20- HETE in Cardiac Pathophysiology: G-Protein-Coupled Receptors, Pharmacological Inhibitors, and Transgenic Approaches.

摘要: ABSTRACT Arachidonic acid-derived lipid mediators play crucial roles in the development and progression of cardiovascular diseases. Eicosanoid metabolites generated by lipoxygenases cytochrome P450 enzymes produce several classes molecules, including epoxyeicosatrienoic acid (EET) hydroxyeicosatetraenoic acids (HETE) family bioactive lipids. In general, cardioprotective effects EETs have been documented across a number cardiac contrast, members HETE shown to contribute pathogenesis ischemic disease, maladaptive hypertrophy, heart failure. The net effect 12(S)- 20-HETE depends upon relative amounts generated, ratio HETEs:EETs produced, timing synthesis, as well cellular subcellular mechanisms activated each respective metabolite. HETEs are synthesized affect multiple cell types within myocardium. Moreover, P450-derived lipoxygenase- derived directly influence myocyte growth regulation fibroblasts. mechanistic data uncovered thus far employed use enzyme inhibitors, antagonists, genetic manipulation lipid-producing their receptors, all which complex network outcomes that complicate interpretation. This review will summarize integrate recent findings on role 12(S)-/20-HETE