Epoxyeicosatrienoic Acids as a Therapeutic Target for Nephropathy Associated with Diabetes and Hypertension

Jeffrey   J.   Olearczyk; John   D.   Imig

Abstract

Nephropathy developing from hypertension and/or non-insulin dependent diabetes mellitus (NIDDM) is becoming increasingly prevalent in the world population. Although there is a significant amount of research being conducted in this area, the etiologies of nephropathy are not known. It has been proposed that hemodynamic and metabolic alterations in the kidney contribute to the development and progression of nephropathy. More interesting however, is the identification of an inflammatory component to nephropathy that is characterized by increased expression of nuclear transcription factors, increased cytokine expression and interstitial cell infiltration. Cytochrome P450 epoxygenase metabolites have recently been reported to regulate sodium excretion as well as renal blood flow and blood pressure. In addition, the epoxyeicosatrienoic acids (EETs) have been identified as anti-inflammatory mediators. We propose that EETs can prevent the development and progression of nephropathy associated with NIDDM and hypertension, by inhibiting the expression of pro-inflammatory genes.

Keywords: cytochrome p-450 metabolites, hypertension, non-insulin dependent diabetes mellitus, inflammation, nuclear factor-kb, monocyte chemoattractant protein-1

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