Determination of Lipoxygenase, CYP450, and Non-Enzymatic Metabolites of Arachidonic Acid in Essential Hypertension and Type 2 Diabetes

Abstract

Type 2 diabetes (T2D) and hypertension (HTN) are common risk factors of cardiovascular diseases (CVD) characterized by chronic low-grade systemic inflammation and impaired endothelial function. This study aimed to assess whether levels of non-enzymatic, lipoxygenase (LOX)- and cytochrome P450 (CYP)-derived arachidonic acid (ARA) metabolites, which are known regulators of vascular homeostasis, are affected by HTN and T2D. For this objective, 17 plasma level derivatives of ARA were quantitated by chromatography coupled with mass spectrometry in 44 patients (12 healthy, 8 HTN, 7 T2D, and 17 HTN + T2D). Effects of hyperglycemic and hyperinsulinemic clamps on ARA metabolite levels were assessed in seven healthy subjects. No significant differences in the plasma levels of ARA metabolites were observed for T2D patients compared with healthy volunteers. HTN was associated with an alteration of ARA metabolite correlation patterns with increased 20-, 19-, 15-, and 8-hydroxyeicosatrienoic acid (HETE). A decrease of 20-HETE was also observed during both hyperglycemic and hyperinsulinemic clamps. Additional experiments are needed to assess whether the modulation of HETE metabolites in HTN may be of interest. Furthermore, although not affected by T2D, it remains to investigate whether the decrease of 20-HETE observed during clamps may be related to the regulation of glucose tolerance and insulin signaling.

Pathophysiology and Outcomes of Endothelium Function in Coronary Microvascular Diseases: A Systematic Review of Randomized Controlled Trials and Multicenter Study

“…Some experimental studies have established the heterogeneous nature of EDH factors by reporting the specific characteristics relating to the different species and vascular beds of concern [ 53 , 54 , 55 ]. Greater production of epoxyeicosatrienoic acids, which constitute the fundamental metabolites of the arachidonic P450 epoxygenase sequential reactions were noted [ 56 , 57 , 58 , 59 , 60 ]. Moreover, the crucial role in electrical communication through gap junctions [ 61 , 62 , 63 ], and unequal production of K + ions [ 64 , 65 , 66 ], hydrogen sulphide (H2S) [ 67 , 68 , 69 , 70 ], monoxide of carbon (CO), [ 71 , 72 ] and endothelium-derived hydrogen peroxide (H 2 O 2 ) [ 73 , 74 ] were observed.…”

Inhibition of Soluble Epoxide Hydrolase Does Not Promote or Aggravate Pulmonary Hypertension in Rats

“…Blood samples were drawn on EDTA tubes, immediately centrifuged (4500× g, 5 min, 4 • C), and the plasma was frozen at −80 • C until analysis. Plasma quantification of EET and DHET regioisomers as well as the levels of EpFAs synthesized by CYP450 from the n-3 docosahexaenoic acid (epoxydocosapentaenoic acids (EpDPAs)) and eicosapentaenoic acid (eicosatetraenoic acids (EpETE)) and from the n-6 linoleic acid (epoxyoctadecenoic acids (EpOMEs)), as well as their respective diols produced by sEH, dihydroxydocosapentaenoic acids (DiHDPA), dihydroxytetraenoic acids (DiHETE), and dihydroxyoctadecenoic acids (DiHOMEs), were quantified using a previously developed liquid chromatography coupled with tandem mass spectrometry method [17].…”