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Cédric Seignez, Mia Phillipson
PURPOSE OF REVIEW: This review describes the mechanisms by which neutrophils contribute to angiogenesis in hypoxic tissues during different conditions and diseases (e.g., menstrual cycle, wound healing, ischemic diseases, cancers), with particular focus on the recently described proangiogenic neutrophil subpopulation. RECENT FINDINGS: The importance of neutrophils in initiation of angiogenesis has been described during the past decade, and is believed to occur through release of the well-known proangiogenic factors Bv8, vascular endothelial growth factor A, and matrix metalloproteinase 9...
October 15, 2016: Current Opinion in Hematology
Yong Zhou, Tian Liu, Jia-Xi Duan, Ping Li, Guo-Ying Sun, Yong-Ping Liu, Jun Zhang, Liang Dong, Kin Sing Stephen Lee, Bruce D Hammcok, Jian-Xin Jiang, Cha-Xiang Guan
Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid (PUFA) with anti-hypertensive, profibrinolytic and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols...
October 6, 2016: Shock
Liang Dong, Yong Zhou, Zhao-Qiong Zhu, Tian Liu, Jia-Xi Duan, Jun Zhang, Ping Li, Bruce D Hammcok, Cha-Xiang Guan
Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. TREM-1 amplifies the inflammatory response. Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 enzyme, have anti-inflammatory properties. However, the effects of EETs on TREM-1 expression under inflammatory stimulation remain unclear. Therefore, inhibition of soluble epoxide hydrolase (sEH) with a highly selective inhibitor [1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, TPPU] was used to stabilize EETs...
October 1, 2016: Inflammation
Christin Boldt, Tom Roeschel, Nina Himmerkus, Allein Plain, Markus Bleich, Robert Labes, Maximilian Blum, Hans Krause, Ahmed Magheli, Torsten Giesecke, Kerim Mutig, Michael Rothe, Steven M Weldon, Duska Dragun, Wolf-Hagen Schunck, Sebastian Bachmann, Alexander Paliege
Activation of the thick ascending limb (TAL) Na+-K+-2Cl--cotransporter (NKCC2) by the antidiuretic hormone arginine-vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5ng/h, 3d) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3...
September 28, 2016: American Journal of Physiology. Renal Physiology
Tomonori Akasaka, Daisuke Sueta, Yuichiro Arima, Noriaki Tabata, Seiji Takashio, Yasuhiro Izumiya, Eiichiro Yamamoto, Megumi Yamamuro, Kenichi Tsujita, Sunao Kojima, Koichi Kaikita, Ayami Kajiwara, Kazunori Morita, Kentaro Oniki, Junji Saruwatari, Kazuko Nakagawa, Yasuhiro Ogata, Kunihiko Matsui, Seiji Hokimoto
BACKGROUND: Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. METHODS AND RESULTS: We examined CYP2C19 genotypes in patients with MVA (n=71) and healthy subjects as control (n=71)...
September 23, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Xuehong Liu, Zu-Yuan Qian, Fuchun Xie, Wei Fan, Jonathan W Nelson, Xiangshu Xiao, Sanjiv Kaul, Anthony P Barnes, Nabil J Alkayed
Epoxyeicosatrienoic acids (EETs) are potent vasodilators that play important roles in cardiovascular physiology and disease, yet the molecular mechanisms underlying the biological actions of EETs are not fully understood. Multiple lines of evidence suggest that the actions of EETs are in part mediated via G protein-coupled receptor (GPCR) signaling, but the identity of such a receptor has remained elusive. We sought to identify 14,15-EET-responsive GPCRs. A set of 105 clones were expressed in Xenopus oocyte and screened for their ability to activate cAMP-dependent chloride current...
September 17, 2016: Prostaglandins & Other Lipid Mediators
Mikhail Romashko, Joseph Schragenheim, Nader G Abraham, John A McClung
Cardiovascular disease remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves epoxyeicosatrienoic acid (EET) and soluble epoxide hydroxylase (sEH) inhibition. sEH is the enzyme that converts EET to its less potent metabolite; therefore, EET is upregulated by its inhibitor. EET has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin sensitivity. Recent reports indicate that EET agonists and sEH inhibitors are capable of not only reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, which is a hallmark of cardiomyopathy and the metabolic syndrome...
September 12, 2016: Trends in Pharmacological Sciences
Vishal R Yadav, Ka L Hong, Darryl C Zeldin, Mohammed A Nayeem
Soluble epoxide hydrolase (sEH) converts epoxyeicosatrienoic acids that are endothelium-derived hyperpolarizing factors into less active dihydroxyeicosatrienoic acids. Previously, we reported a decrease in adenosine A1 receptor (A1AR) protein levels in sEH knockout (sEH(-/-)) and an increase in sEH and A1AR protein levels in A2AAR(-/-) mice. Additionally, KATP channels are involved in adenosine receptor (AR)-dependent vascular relaxation. Thus, we hypothesize that a potential relationship may exist among sEH over-expression, A1AR upregulation, inactivation of KATP channels, and increased in vascular tone...
November 2016: Molecular and Cellular Biochemistry
Mohamed M Katary, Chelsey Pye, Ahmed A Elmarakby
The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n=6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months...
September 2, 2016: Prostaglandins & Other Lipid Mediators
Yunxiao Li, Ganggang Yu, Shaopeng Yuan, Chunting Tan, Jianlin Xie, Yasi Ding, Puqiao Lian, Lixia Fu, Qi Hou, Bo Xu, Haoyan Wang
BACKGROUND/AIMS: Epoxyeicosatrienoic acids (EETs) are metabolic products of free arachidonic acid (AA). EETs have anti-inflammatory activities. However, the effect of EETs on cigarette smoke-induced lung inflammation is not clear. Autophagy is believed to be involved in the pathogenesis of COPD. In addition, nuclear erythroid-related factor 2 (Nrf2), is thought to regulate antioxidant defenses in several lung diseases. Besides, interaction between EETs, autophagy and Nrf2 has been reported...
September 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Christophe Morisseau, Mohammed A Nayeem
Coronary reactive hyperemia (CRH) is a physiological response to ischemic insult that prevents the potential harm associated with an interruption of blood supply. The relationship between the pharmacologic inhibition of soluble epoxide hydrolase (sEH) and CRH response to a brief ischemia is not known. sEH is involved in the main catabolic pathway of epoxyeicosatrienoic acids (EETs), which are converted into dihydroxyeicosatrienoic acids (DHETs). EETs protect against ischemia/reperfusion injury and have numerous beneficial physiological effects...
2016: PloS One
Takeshi Y Hiyama, Masaharu Noda
The brain monitors conditions of body fluids and levels of circulating neuroactive factors to maintain the systemic homeostasis. Unlike most regions in the brain, circumventricular organs (CVOs) lack the blood-brain barrier, and serve as the sensing center. Among the CVOs, the subfornical organ (SFO) is the sensing site of Na(+) levels in body fluids to control water and salt intake. The SFO harbors neuronal cell bodies with a variety of hormone receptors and innervates many brain loci. In addition, the SFO harbors specialized glial cells (astrocytes and ependymal cells) expressing Nax, a Na(+)-level-sensitive sodium channel...
August 10, 2016: Neuroscience Research
M Hamzaoui, C Roche, A Lejeune, V Brunel, V Richard, J Bellien, D Guerrot
OBJECTIVE: Cardiovascular (CV) events are more prevalent in chronic kidney disease (CKD) than in the general population, being the main cause of morbi-mortality. The aim of this project is to study the CV impact of the increase in the bioavailability of epoxyeicosatrienoic acids (EETs) by inhibiting soluble epoxide hydrolase (sEH) in the 5/6 nephrectomy model in 129/Sv mice. DESIGN AND METHOD: 5/6 Nx mice were treated with the sEH inhibitor t-AUCB, a diuretic (amiloride), or placebo for 10 weeks...
September 2016: Journal of Hypertension
Clémence O Henry, Emilie Dalloneau, Maria-Teresa Pérez-Berezo, Cristina Plata, Yongzheng Wu, Antoine Guillon, Eric Morello, Rose-France Aimar, Marie Potier-Cartereau, Frédéric Esnard, Christelle Coraux, Christian Börnchen, Rainer Kiefmann, Christophe Vandier, Lhousseine Touqui, Miguel A Valverde, Nicolas Cenac, Mustapha Si-Tahar
Cystic fibrosis (CF) is an inherited disease associated with chronic severe lung inflammation, leading to premature death. To develop innovative anti-inflammatory treatments, we need to characterize new cellular and molecular components contributing to the mechanisms of lung inflammation. Here, we focused on the potential role of "transient receptor potential vanilloid-4" (TRPV4), a nonselective calcium channel. We used both in vitro and in vivo approaches to demonstrate that TRPV4 expressed in airway epithelial cells triggers the secretion of major proinflammatory mediators such as chemokines and biologically active lipids, as well as a neutrophil recruitment in lung tissues...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Dan Li, Yajin Liu, Xu Zhang, Huizhen Lv, Wei Pang, Xiaoli Sun, Li-Ming Gan, Bruce D Hammock, Ding Ai, Yi Zhu
RATIONALE: Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE: We aimed to investigate the effect of sEH inhibition in atherogenesis. METHODS AND RESULTS: Mice with low-density lipoprotein receptor deficiency (Ldlr(-/-)) with or without sEH inhibitor, and Ldlr/sEH double-knockout (DK) mice were fed a Western-type diet (WTD) for 6weeks to induce arteriosclerosis...
September 2016: Journal of Molecular and Cellular Cardiology
Haitham E El-Sikhry, Nasser Alsaleh, Rambabu Dakarapu, John R Falck, John M Seubert
Maintenance of a healthy pool of mitochondria is important for the function and survival of terminally differentiated cells such as cardiomyocytes. Epoxyeicosatrienoic acids (EETs) are epoxy lipids derived from metabolism of arachidonic acid by cytochrome P450 epoxygenases. We have previously shown that EETs trigger a protective response limiting mitochondrial dysfunction and reducing cellular death. The aim of this study was to investigate whether EET-mediated effects influence mitochondrial quality in HL-1 cardiac cells during starvation...
2016: PloS One
Wei Tao, Ping-Song Li, Liu-Qing Yang, Yong-Bo Ma
OBJECTIVES: Inflammation plays a key role in the pathogenesis of acute lung injury (ALI). Soluble epoxide hydrolase (sEH) is suggested as a vital pharmacologic target for inflammation. In this study, we determined whether a sEH inhibitor, AUDA, exerts lung protection in lipopolysaccharide (LPS)-induced ALI in mice. METHODS: Male BALB/c mice were randomized to receive AUDA or vehicle intraperitoneal injection 4 h after LPS or phosphate buffered saline (PBS) intratracheal instillation...
2016: PloS One
Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Christophe Morisseau, Mohammed A Nayeem
The relationship between soluble epoxide hydrolase (sEH) and coronary reactive hyperemia (CRH) response to a brief ischemic insult is not known. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia/reperfusion injury. sEH converts EETs into dihydroxyeicosatrienoic-acids (DHETs). Therefore, we hypothesized that knocking out sEH enhances CRH through modulation of oxylipin profiles, including an increase in EET/DHET ratio. Compared with sEH(+/+), sEH(-/-) mice showed enhanced CRH, including greater repayment volume (RV; 28% higher, P < 0...
October 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Chi Zhou, Jin Huang, Junxiong Chen, Jinsheng Lai, Fasheng Zhu, Xizhen Xu, Dao Wen Wang
BACKGROUND: Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acids (AA) to form epoxyeicosatrienoic acids (EETs), which exert beneficial roles in the treatment of cardiovascular diseases, but little is known about its role on adventitial remodeling. METHODS: We used C57BL/6J mice in vivo and primary rat adventitial fibroblasts (AFs) in vitro treated with Angiotensin II to investigate the effects of CYP2J2 gene delivery and exogenous EETs administration on adventitial remodeling...
2016: Cellular Physiology and Biochemistry
J D Imig
Endothelial and vascular smooth cells generate cytochrome P450 (CYP) arachidonic acid metabolites that can impact endothelial cell function and vascular homeostasis. The objective of this review is to focus on the physiology and pharmacology of endothelial CYP metabolites. The CYP pathway produces two types of eicosanoid products: epoxyeicosatrienoic acids (EETs), formed by CYP epoxygenases, and hydroxyeicosatetraenoic acids (HETEs), formed by CYP hydroxylases. Advances in CYP enzymes, EETs, and 20-HETE by pharmacological and genetic means have led to a more complete understanding of how these eicosanoids impact on endothelial cell function...
2016: Advances in Pharmacology
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