Journal
JOURNAL OF LIPID RESEARCH
Volume 59, Issue 11, Pages 2047-2062Publisher
ELSEVIER
DOI: 10.1194/jlr.R087882
Keywords
eicosanoids; diseases; genetics; kidney; endothelial cells; PPAR
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [P01-038226]
- National Institute of General Medical Sciences [R01-037922, R01-031278]
- National Institutes of Health [LR01-0139793]
- Welch Foundation [I-0011]
- Dr. Ralph and Marian Falk Medical Research Trust
Ask authors/readers for more resources
The initial studies of the metabolism of arachidonic acid (AA) by the cytochrome P450 (P450) hemeproteins sought to: a) elucidate the roles for these enzymes in the metabolism of endogenous pools of the FA, b) identify the P450 isoforms involved in AA epoxidation and omega/omega-1 hydroxylation, and c) explore the biological activities of their metabolites. These early investigations provided a foundation for subsequent efforts to establish the physiological relevance of the AA monooxygenase and its contributions to the pathophysiology of, for example, cancer, diabetes, hypertension, inflammation, nociception, and vascular disease. This retrospective analyzes the history of some of these efforts, with emphasis on genetic studies that identified roles for the murine Cyp4a and Cyp2c genes in renal and vascular physiology and the pathophysiology of hypertension and cancer. Wide-ranging investigations by laboratories worldwide, including the authors, have established a better appreciation of the enzymology, genetics, and physiologic roles for what is now known as the third branch of the AA cascade. Combined with the development of analytical and pharmacological tools, including robust synthetic agonists and antagonists of the major metabolites, we stand at the threshold of novel therapeutic approaches for the treatment of renal injury, pain, hypertension, and heart disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available