Unraveling the Role of 12- and 20- HETE in Cardiac Pathophysiology: G-Protein-Coupled Receptors, Pharmacological Inhibitors, and Transgenic Approaches
| Autor: | Pamela A Lucchesi, Jonathan V. Pascale, Victor Garcia |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Myocardial Ischemia Cardiomegaly 030204 cardiovascular system & hematology Epoxyeicosatrienoic acid Receptors G-Protein-Coupled Animals Genetically Modified 03 medical and health sciences chemistry.chemical_compound Lipoxygenase 0302 clinical medicine Cytochrome P-450 Enzyme System Hydroxyeicosatetraenoic Acids Animals Humans 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid Receptor G protein-coupled receptor Pharmacology Heart Failure biology Cardiac myocyte Hydroxyeicosatetraenoic acid Lipid signaling Cell biology 030104 developmental biology chemistry Eicosanoid Cardiovascular Diseases cardiovascular system biology.protein lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of cardiovascular pharmacology. 77(6) |
| ISSN: | 1533-4023 |
| Popis: | Arachidonic acid-derived lipid mediators play crucial roles in the development and progression of cardiovascular diseases. Eicosanoid metabolites generated by lipoxygenases and cytochrome P450 enzymes produce several classes of molecules, including the epoxyeicosatrienoic acid (EET) and hydroxyeicosatetraenoic acids (HETE) family of bioactive lipids. In general, the cardioprotective effects of EETs have been documented across a number of cardiac diseases. In contrast, members of the HETE family have been shown to contribute to the pathogenesis of ischemic cardiac disease, maladaptive cardiac hypertrophy, and heart failure. The net effect of 12(S)- and 20-HETE depends upon the relative amounts generated, ratio of HETEs:EETs produced, timing of synthesis, as well as cellular and subcellular mechanisms activated by each respective metabolite. HETEs are synthesized by and affect multiple cell types within the myocardium. Moreover, cytochrome P450-derived and lipoxygenase- derived metabolites have been shown to directly influence cardiac myocyte growth and the regulation of cardiac fibroblasts. The mechanistic data uncovered thus far have employed the use of enzyme inhibitors, HETE antagonists, and the genetic manipulation of lipid-producing enzymes and their respective receptors, all of which influence a complex network of outcomes that complicate data interpretation. This review will summarize and integrate recent findings on the role of 12(S)-/20-HETE in cardiac diseases. |
| Databáze: | OpenAIRE |
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