Effect of human 15-lipoxygenase-1 metabolites on vascular function in mouse mesenteric arteries and hearts

Kriska, Tamás; Cepura, Cody; Siangjong, Lawan; Wan, Tina C.; Auchampach, John A.; Shaish, Aviv; Haratz, D.; Kumar, Ganesh; Falck, John R.; Gauthier, Kathryn M.; Campbell, William B.

doi:10.1016/j.prostaglandins.2013.07.002

Cited by 7 publications

(8 citation statements)

References 41 publications

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“…It is important to note that the basal coronary flow we recorded in WT hearts (~1.7 mL/min) was lower than that reported by others (Kriska et al. ). This is possibly due to the fact that in comparison with the natural heart rate of ~320 beat/min in our studies, the referenced studies of others used pacing hearts in their research, which led to a corresponding heart rate of 420 beats/min (Kriska et al.…”

Section: Discussioncontrasting

confidence: 75%

Inhibition of soluble epoxide hydrolase increases coronary perfusion in mice

et al. 2015

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Roles of soluble epoxide hydrolase (sEH), the enzyme responsible for hydrolysis of epoxyeicosatrienoic acids (EETs) to their diols (DHETs), in the coronary circulation and cardiac function remain unknown. We tested the hypothesis that compromising EET hydrolysis/degradation, via sEH deficiency, lowers the coronary resistance to promote cardiac perfusion and function. Hearts were isolated from wild type (WT), sEH knockout (KO) mice and WT mice chronically treated with t-TUCB (sEH inhibitor), and perfused with constant flow at different pre-loads. Compared to WT controls, sEH-deficient hearts required significantly greater basal coronary flow to maintain the perfusion pressure at 100 mmHg and exhibited a greater reduction in vascular resistance during tension-induced heart work, implying a better coronary perfusion during cardiac performance. Cardiac contractility, characterized by developed tension in response to changes in preload, was potentially increased in sEH-KO hearts, manifested by an enlarged magnitude at each step-wise increase in end-diastolic to peak-systolic tension. 14,15-EEZE (EET antagonist) prevented the adaptation of coronary circulation in sEH null hearts whereas responses in WT hearts were sensitive to the inhibition of NO. Cardiac expression of EET synthases (CYP2J2/2C29) was comparable in both genotypic mice whereas, levels of 14,15-, 11,12- and 8,9-EETs were significantly higher in sEH-KO hearts, accompanied with lower levels of DHETs. In conclusion, the elevation of cardiac EETs, as a function of sEH deficiency, plays key roles in the adaptation of coronary flow and cardiac function.

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Section: Discussioncontrasting

confidence: 75%

Inhibition of soluble epoxide hydrolase increases coronary perfusion in mice

et al. 2015

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“…However, there was a difference in the basal HETE levels in plasma from WT and KI mice. HETEs can cause vasorelaxation (35,36), and therefore their decreased abundance in KI plasma provides an explanation for their basal hypertension compared with littermate WT. What remains undefined is the mechanism by which plasma HETE levels are lower in KI.…”

Section: Discussionmentioning

confidence: 99%

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

Charles

Rudyk

Prysyazhna

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center. This inhibition prevents hydrolysis of the enzymes' epoxyeicosatrienoic acid (EET) substrates, so they accumulate inducing vasodilation to lower blood pressure (BP). We generated a Cys521Ser sEH redoxdead knockin (KI) mouse model that was resistant to this mode of inhibition. The electrophilic lipid 10-nitro-oleic acid (NO 2 -OA) inhibited hydrolase activity and also lowered BP in an angiotensin II-induced hypertension model in wild-type (WT) but not KI mice. Furthermore, EET/dihydroxy-epoxyeicosatrienoic acid isomer ratios were elevated in plasma from WT but not KI mice following NO 2 -OA treatment, consistent with the redox-dead mutant being resistant to inhibition by lipid electrophiles. sEH was inhibited in WT mice fed linoleic acid and nitrite, key constituents of the Mediterranean diet that elevates electrophilic nitro fatty acid levels, whereas KIs were unaffected. These observations reveal that lipid electrophiles such as NO 2 -OA mediate antihypertensive signaling actions by inhibiting sEH and suggest a mechanism accounting for protection from hypertension afforded by the Mediterranean diet.thiol | cardiovascular

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“…12-15LO metabolites are known to be involved in ACh-induced arterial relaxation in mesenteric arteries and may be involved in the increase in splanchnic blood flow of portal hypertension [120,121]. Moreover transgenic mice that overexpress 15-LO and rabbits infected with adenovirus containing cDNA for human 15-LO have an increased ACh-and AA-mediated relaxation in mesenteric arteries as compared to control animals [120,121].…”

Section: Lipoxygenase-dependent Aa Metabolitesmentioning

confidence: 99%

“…Moreover transgenic mice that overexpress 15-LO and rabbits infected with adenovirus containing cDNA for human 15-LO have an increased ACh-and AA-mediated relaxation in mesenteric arteries as compared to control animals [120,121]. Because of the increased response to ACh [122] in cirrhosis, a role of 15LO metabolites in the pathological vasodilatation of arterial splanchnic vessels in liver cirrhosis can be hypothesized.…”

Section: Lipoxygenase-dependent Aa Metabolitesmentioning

confidence: 99%

Arachidonic acid metabolites and endothelial dysfunction of portal hypertension

Sacerdoti

Paterini

Pascoli

et al. 2015

Prostaglandins & Other Lipid Mediators

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Increased resistance to portal flow and increased portal inflow due to mesenteric\ud vasodilatation represent the main factors causing portal hypertension in\ud cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the\ud synthesis, release, and effect of endothelial mediators of vascular tone,\ud inflammation, thrombosis, and angiogenesis, plays a major role in the increase of\ud resistance in portal circulation, in the decrease in the mesenteric one, in the\ud development of collateral circulation. Reduced response to vasodilators in liver \ud sinusoids and increased response in the mesenteric arterioles, and, viceversa,\ud increased response to vasoconstrictors in the portal-sinusoidal circulation and\ud decreased response in the mesenteric arterioles are also relevant to the\ud pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through\ud the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450\ud monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal \ud hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial\ud cells (LSECs) via increased COX-1 activity/expression, increased leukotriens,\ud increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial\ud circulation, but vasoconstrictors of the portal-sinusoidal circulation),\ud represent a major component in the increased portal resistance, in the decreased \ud portal response to vasodilators and in the hyper-response to vasoconstrictors.\ud Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased\ud EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived\ud hyperpolarizing factor system) play a major role in mesenteric vasodilatation,\ud hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs,\ud mediators of liver regeneration after hepatectomy and of angiogenesis, may play a\ud role in the development of regenerative nodules and collateral circulation,\ud through stimulation of vascular endothelial growth factor (VEGF) inside the liver\ud and in the portal circulation. Pharmacological manipulation of AA metabolites may\ud be beneficial for cirrhotic portal hypertension

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Effect of human 15-lipoxygenase-1 metabolites on vascular function in mouse mesenteric arteries and hearts

Cited by 7 publications

References 41 publications

Inhibition of soluble epoxide hydrolase increases coronary perfusion in mice

Inhibition of soluble epoxide hydrolase increases coronary perfusion in mice

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

Arachidonic acid metabolites and endothelial dysfunction of portal hypertension

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