Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice

Abstract

BackgroundEicosapentaenoic acid (EPA) is thought to have many beneficial effects, such as anti-atherosclerogenic and anti-inflammatory properties. However, few studies have reported its effects of endothelial dysfunction in diabetes and its direct effects on the aorta. Here, we investigated the effects of EPA treatment on impaired endothelium-dependent relaxation of the aorta in KKAy mice, a model of type 2 diabetes.MethodsMale KKAy mice were fed a high-fat (HF) diet for 8 weeks to induce diabetes, after which they were divided into two groups. One group was fed a HF diet, and the other group was fed a HF diet containing EPA ethyl ester (EPA-E, 10 mg/day) for 4 weeks. Then, the vascular reactivities of prepared aortic rings were measured in an organ bath to determine if EPA-E administration changed vascular function in these diabetic mice. In addition, we examined effect of EPA-E and its metabolites to vascular action using aorta separated from C57BL/6 J mice.ResultsAlthough EPA-E administration did not change the plasma glucose and insulin levels in diabetic mice, total cholesterol levels were significantly decreased. The aorta extracted from EPA-E untreated diabetic mice showed impaired endothelium-dependent relaxation in response to acetylcholine (ACh). However, EPA-E administration improved the relaxation response to ACh to the control levels observed in non-diabetic C57BL/6 J mice. On the other hand, endothelium-independent relaxation in response to sodium nitroprusside did not significantly differ among these three groups. The enhanced contractile response by phenylephrine in diabetic mice was not altered by the administration of EPA-E. In addition, the direct administration of EPA-E metabolites such as EPA, docosahexaenoic acid, and docosapentaenoic acid led to vasodilation in the aortic rings of C57BL/6 J mice.ConclusionThese results showed that chronic EPA-E administration prevented the development of endothelial dysfunction in KKAy mice, partly via the direct action of EPA-E metabolites on the aorta.

Clinacanthus nutans Leaves Extract Reverts Endothelial Dysfunction in Type 2 Diabetes Rats by Improving Protein Expression of eNOS

“…Phenylephrine, an α -adrenergic receptor agonist stimulates Ca 2+ entry through voltage-gated and store-operated Ca 2+ channels and activates Ca 2+ sensitization pathways such as protein kinase-C (PKC) and Rho-kinase [ 36 ]. Activation of PKC increases the myofilament force sensitivity to cytosolic Ca 2+ concentration and myosin light-chain (MLC) phosphorylation and thereby maintains VSMC contraction with smaller increases in cytosolic Ca 2+ concentration [ 37 ].…”

Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells

“…There is growing evidence that n-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish oil-especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-can improve lipid metabolism and blood lipid profiles, prevent the progression of atherosclerosis, and reduce the incidence of cardiovascular diseases [7] as well as liver and plasma triglyceride levels [8]. We previously demonstrated that chronic oral administration of EPA prevented endothelial dysfunction in a mouse model of type 2 diabetes [9]. n-3 PUFAs have also been reported to have various anti-cancer effects in several types of malignancy in vitro and in vivo.…”

Effect of the double bond conjugation on the vascular physiology and nitric oxide production of isomers of eicosapentaenoic and docosahexaenoic acids prepared from shark oil

“…Direct administration of EPA and other metabolites induced relaxation in the aorta ring isolated from C57BL/6J mice. The relaxation activity is reported by the authors as endothelium independent [64].…”

“…The authors concluded that CYP450 (cytochrome P450) and IKCa (K+ and Na+ channel) receptors are related to the induction of vasodilation by EPA in the mesenteric artery, while IKCa could be implicated in the relaxation exerted by DHA in the aorta [30]. Takenouchi et al [64] studied the effect of EPA ethyl ester (EPA-E) supplementation in the diabetic KKAy (transcription factor kayak) mouse and nondiabetic C57BL/6 mouse (10 mg/day, 4 weeks). Interestingly, after treatment, aorta rings isolated from nondiabetic C57BL/6 mice fed EPA-E improved the vasodilation exerted by ACh.…”