Effects of Eicosapentaenoic Acid on Endothelial Cell-Derived Microparticles, Angiopoietins and Adiponectin in Patients with Type 2 Diabetes

Nomura, Shosaku; Shouzu, Akira; Omoto, Seitaro; Inami, Norihito; Ueba, Tetsuya; Urase, Fumiaki; Maeda, Yasuhiro

doi:10.5551/jat.e091

Cited by 55 publications

(52 citation statements)

References 50 publications

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“…We speculate that anti-inflammatory effects of EPA might be principally responsible for reducing atherosclerotic lesions and prevent cardiovascular events 15,[19][20][21][22][23][24][25] . Concerning the prevention of CAD by EPA as well as its anti-inflammatory effect, it should be noted that EPA exhibits an antiarrhythmic effect 26) , inhibits platelet aggregation 27,28) , exhibits vasodilatory activity 29) , increases the circulating adiponectin level 30) , has a triglyceride-lowering effect 31) , and induces plaque stabilization 24,32) . These effects may function synergistically to prevent CAD.…”

Section: Discussionmentioning

confidence: 99%

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

Itakura¹,

Yokoyama

Matsuzaki

et al. 2011

JAT

202

146

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Aim:The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. Methods: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/ stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. Results: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio 0.83, p 0.049, in all participants and hazard ratio 0.71, p 0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 g/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 g/mL) group. Conclusion: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events. J Atheroscler Thromb, 2011; 18:99-107.

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Section: Discussionmentioning

confidence: 99%

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

Itakura¹,

Yokoyama

Matsuzaki

et al. 2011

JAT

202

146

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“…49 Moreover, diabetic patients treated with eicosapentaenoic acid showed a significant decrease of their EMP plasma concentrations. 50 In patients with metabolic syndrome, pioglitazone administration diminished EMP levels. 51 Intravitreal anti-vascular endothelial growth factor injection decreased vitreous EMP shed following proliferative diabetic retinopathy.…”

Section: Dignat-george and Boulangermentioning

confidence: 99%

The Many Faces of Endothelial Microparticles

Dignat-George

Boulanger

2011

ATVB

555

495

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Abstract-Endothelial microparticles (EMP) are complex vesicular structures shed from activated or apoptotic endothelial cells. They play a remarkable role in coagulation, inflammation, endothelial function, and angiogenesis and thus disturb the vascular homeostasis, contributing to the progression of vascular diseases. As a cause or a consequence, elevated levels of EMP were found in plasma from patients with vascular diseases, where they serve as a surrogate marker of endothelial function. More recent data challenged the presumed deleterious role of EMP because they could promote cell survival, exert antiinflammatory effects, counteract coagulation processes, or induce endothelial regeneration. This review focuses on the ambivalent role of EMP in vascular homeostasis. (Arterioscler Thromb Vasc Biol. 2011;31:27-33.)Key Words: apoptosis Ⅲ atherosclerosis Ⅲ endothelial function Ⅲ endothelium Ⅲ thrombin Ⅲ thrombosis Ⅲ vascular biology Ⅲ microparticles V ascular endothelial cells, like most cells, release different types of membrane vesicles, including microparticles (MP) and exosomes, in response to cellular activation or apoptosis. In addition, apoptotic bodies might be generated during the final steps of programmed cell death. These different vesicles are distinguished from one another on the basis of their subcellular origin, their size, their content, the mechanisms leading to their formation, and, from a practical point of view, how they are obtained. Endothelial Microparticle CharacteristicsEndothelial microparticles (EMP) (Ϸ100 nm to 1 m in diameter) result from endothelial plasma membrane blebbing and carry endothelial proteins such as vascular endothelial cadherin, platelet endothelial cell adhesion molecule-1, intercellular cell adhesion molecule (ICAM)-1, endoglin, E-selectin, S-endo or ␣v integrin (Figure 1). 1 Endothelial NO synthase and vascular endothelial growth factor receptor (VEGF-R2) have also been identified on EMP, 2 but there is so far no evidence on whether or not MP endothelial nitric oxide synthase is capable of generating nitric oxide; furthermore, endothelial nitric oxide synthase may also be present on platelet or red blood cell-derived MP. E-selectin (CD62E) is expressed by activated endothelial cells but can equally be found on EMP generated following either tumor necrosis factor-␣ (TNF-␣) activation or growth factor deprivationinduced apoptosis. 3 Identification of endothelial origin of circulating MP relies on the use of specific markers for flow cytometry analysis (see below); unfortunately, except E-selectin and vascular endothelial cadherin, most of them lack exclusive endothelial expression. Endoglin (CD105) is also expressed by activated monocytes/macrophages and bone marrow cell subsets; platelet endothelial cell adhesion molecule-1 (CD31) is present on activated platelets, platelet MP, and leukocyte subsets; S-endo (CD146) has been found on pericytes, tumor cells, and activated T-cells; ICAM-1 (CD54) is also expressed by leukocytes; and ␣v integrin (CD51) is present on monocy...

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“…Studies investigating EPAs effects on hyperlipidemic volunteers with diabetes revealed significant decreases in endothelial microvesicles following 6 months of treatment. Non-diabetic patients however, showed no change in endothelial microvesicles concentrations [56][57][58][59].…”

Section: Effect Of Metabolic Disease Medications On Microvesiclesmentioning

confidence: 84%

Microvesicles as Biomarkers in Diabetes, Obesity and Non-Alcoholic Fatty Liver Disease: Current Knowledge and Future Directions

Welsh

Holloway²,

Englyst³

2014

Intern Med

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NAFLD is the most common chronic liver disease, frequently associated with diabetes. Both of these insulin resistant states have increased cardiovascular risk factors associated, and a prevalent cause of mortality in these diseases. Microvesicles are heterogonously sized, phospholipid rich spheres released by cells upon activation and apoptosis. Evidence is continuing to accumulate of microvesicles being not only markers of disease severity but as also having a functional role in the pathophysiology of disease progression.

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Effects of Eicosapentaenoic Acid on Endothelial Cell-Derived Microparticles, Angiopoietins and Adiponectin in Patients with Type 2 Diabetes

Cited by 55 publications

References 50 publications

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

The Many Faces of Endothelial Microparticles

Microvesicles as Biomarkers in Diabetes, Obesity and Non-Alcoholic Fatty Liver Disease: Current Knowledge and Future Directions

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