Soluble epoxide hydrolase inhibition improves myocardial perfusion and function in experimental heart failure

Merabet, Nassiba; Bellien, Jérémy; Glevarec, Etienne; Nicol, Lionel; Lucas, Danièle; Rémy-Jouet, Isabelle; Bounoure, F.; Dréano, Yvonne; Wecker, Didier; Thuillez, Christian; Mulder, Paul

doi:10.1016/j.yjmcc.2011.11.015

Cited by 60 publications

(47 citation statements)

References 36 publications

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“…Endothelium-independent relaxations to the NO donor sodium nitroprusside (10 Ϫ9 to 10 Ϫ4.5 M) and the coronary relaxing responses to NS1619, an opener of large-conductance calcium-activated potassium (BK Ca) channels (10 Ϫ6 to 10 Ϫ4.5 M), which are the main smooth muscle cellular targets of EETs mediating their hyperpolarizing effect, and to NS309, an opener of SKCa and IKCa channels (10 Ϫ8 to 10 Ϫ5 M), were assessed (3,8). Coronary protein expressions of eNOS, sEH, and BK Ca channels were determined by Western blot analysis, and results were normalized to actin level (8,18). Cardiac evaluations.…”

Section: Methodsmentioning

confidence: 99%

“…Cardiac evaluations. In mice anesthetized with isoflurane (1% to 2%), left ventricular (LV) dimensions, and function were assessed at W0, W8, and W16, using a Vivid 7 ultrasound device (GE medical) (8,18). The heart was imaged in the two-dimensional mode in the parasternal short-axis view.…”

Section: Methodsmentioning

confidence: 99%

“…Myocardial perfusion was assessed at W16 by cardiac magnetic resonance imaging (MRI) in anesthetized mice using a 4.7 T horizontal bore scanner (Bruker) and the arterial spin labeling technique (18).…”

Section: Methodsmentioning

confidence: 99%

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Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice

Roche

Besnier

Cassel

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Ouvrard-Pascaud A, Madec A, Richard V, Bellien J. Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice. Am J Physiol Heart Circ Physiol 308: H1020 -H1029, 2015. First published February 25, 2015; doi:10.1152/ajpheart.00465.2014.-This study addressed the hypothesis that inhibiting the soluble epoxide hydrolase (sEH)-mediated degradation of epoxy-fatty acids, notably epoxyeicosatrienoic acids, has an additional impact against cardiovascular damage in insulin resistance, beyond its previously demonstrated beneficial effect on glucose homeostasis. The cardiovascular and metabolic effects of the sEH inhibitor trans-4- [4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB; 10 mg/l in drinking water) were compared with those of the sulfonylurea glibenclamide (80 mg/l), both administered for 8 wk in FVB mice subjected to a high-fat diet (HFD; 60% fat) for 16 wk. Mice on control chow diet (10% fat) and nontreated HFD mice served as controls. Glibenclamide and t-AUCB similarly prevented the increased fasting glycemia in HFD mice, but only t-AUCB improved glucose tolerance and decreased gluconeogenesis, without modifying weight gain. Moreover, t-AUCB reduced adipose tissue inflammation, plasma free fatty acids, and LDL cholesterol and prevented hepatic steatosis. Furthermore, only the sEH inhibitor improved endothelium-dependent relaxations to acetylcholine, assessed by myography in isolated coronary arteries. This improvement was related to a restoration of epoxyeicosatrienoic acid and nitric oxide pathways, as shown by the increased inhibitory effects of the nitric oxide synthase and cytochrome P-450 epoxygenase inhibitors L-NA and MSPPOH on these relaxations. Moreover, t-AUCB decreased cardiac hypertrophy, fibrosis, and inflammation and improved diastolic function, as demonstrated by the increased E/A ratio (echocardiography) and decreased slope of the end-diastolic pressure-volume relation (invasive hemodynamics). These results demonstrate that sEH inhibition improves coronary endothelial function and prevents cardiac remodeling and diastolic dysfunction in obese insulin-resistant mice. insulin resistance; soluble epoxide hydrolase; endothelium; cardiac function ENDOTHELIAL DYSFUNCTION AND accelerated atherosclerosis, secondary to the chronic pro-inflammatory state generated by hyperinsulinemia, hyperglycemia, and dyslipidemia, play a critical role in the development of cardiovascular complications of type 2 diabetes (12,17,22). Strategies for multiple risk-factor control including glucose, lipid, and blood pressure levels have shown a clear benefit on cardiovascular outcome in type 2 diabetic patients (22, 23). However, these patients are still at increased cardiovascular risk, and new therapeutic targets are needed (22,23).In this context, pharmacological therapies targeting both the metabolic and cardiovascular abnormalities in type 2 diabetes would be ideal candidates. An emerging pharmacological app...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice

Roche

Besnier

Cassel

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

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“…For example, EETs and a soluble epoxide hydrolase inhibitor have been demonstrated to reduce infract size during I/R and improve cardiac function by preventing cardiac fibrosis (20,41,42). In contrast, cardiac overexpression of 12/15-LOX was reported to result in systolic dysfunction, inflammation, cardiac fibrosis, and macrophage infiltration (43,44).…”

Section: Discussionmentioning

confidence: 99%

Heart failure–induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore

Moon

Liu

Cedars

et al. 2018

Journal of Biological Chemistry

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2 ) identified by sequential column chromatographies and activity-based protein profiling. In contrast, iPLA 2 ␥ predominated in failing human myocardium. Stable isotope kinetics revealed that in non-failing human hearts, cPLA 2 metabolically channels arachidonic acid into EETs, whereas in failing hearts, increased iPLA 2 ␥ activity channels AA into toxic HETEs. These results mechanistically identify the sequelae of pathological remodeling of human mitochondrial phospholipases in failing myocardium. This remodeling metabolically channels AA into toxic HETEs promoting mPTP opening, which induces necrosis/apoptosis leading to further progression of heart failure.

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“…Cardiac MRI was performed with a 4.7-T horizontal bore scanner (Biospin MRI; Bruker, Ettlingen, Germany) [29,30] in mice anesthetized by intraperitoneal injection of 320 mg kg À1 chloral hydrate (Sigma-Aldrich, Lyon, France). Cardiac perfusion was evaluated in the noninfarcted LV area with the arterial spin-labeling technique [31], in which the blood in the arteries upstream from the imaging volume is magnetically labeled.…”

Section: Cardiac Magnetic Resonance Imaging (Mri)mentioning

confidence: 99%

Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura

Besnerais

Favre

Denis

et al. 2016

Journal of Thrombosis and Haemostasis

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Soluble epoxide hydrolase inhibition improves myocardial perfusion and function in experimental heart failure

Cited by 60 publications

References 36 publications

Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice

Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice

Heart failure–induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore

Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura

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