Whatever Happened to the Epoxyeicosatrienoic Acid-Like Endothelium-Derived Hyperpolarizing Factor? The Identification of Novel Classes of Lipid Mediators and Their Role in Vascular Homeostasis

Frömel, Timo; Fleming, Ingrid

doi:10.1089/ars.2014.6150

Cited by 21 publications

(11 citation statements)

References 196 publications

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“…Disulfide activation of PKG Iα by dimerization mediates relaxation of bovine coronary arteries to hypoxia, which was also associated with oxidation of cytosolic NADPH and phosphorylation of the PKG substrate protein vasodilator-stimulated phosphoprotein (VASP; Neo et al, 2011 ; Figure 2 ). Although these data support PKG Iα oxidation as a mechanism of EDHF-dependent vasodilation, it is notable that the evidence for other factors such as epoxyeicosatrienoic acids (EETs) being a principal mediator is especially robust ( Fromel and Fleming, 2015 ). Although it is interesting to note that the epoxide moiety present in EETs can have thiol reactivity, leading to the idea that these lipid species could potentially react with C42 of PKG Iα to activate it.…”

Section: The Role Of Pkg Iα Disulfide Dimerisation In Blood Vesselsmentioning

confidence: 98%

Redox regulation of cGMP-dependent protein kinase Iα in the cardiovascular system

Prysyazhna

Eaton

2015

Front. Pharmacol.

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Elevated levels of oxidants in biological systems have been historically referred to as “oxidative stress,” a choice of words that perhaps conveys an imbalanced view of reactive oxygen species in cells and tissues. The term stress suggests a harmful role, whereas a contemporary view is that oxidants are also crucial for the maintenance of homeostasis or adaptive signaling that can actually limit injury. This regulatory role for oxidants is achieved in part by them inducing oxidative post-translational modifications of proteins which may alter their function or interactions. Such mechanisms allow changes in cell oxidant levels to be coupled to regulated alterations in enzymatic function (i.e., signal transduction), which enables “redox signaling.” In this review we focus on the role of cGMP-dependent protein kinase (PKG) Ia disulfide dimerisation, an oxidative modification that is induced by oxidants that directly activates the enzyme, discussing how this impacts on the cardiovascular system. Additionally, how this oxidative activation of PKG may coordinate with or differ from classical activation of this kinase by cGMP is also considered.

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Section: The Role Of Pkg Iα Disulfide Dimerisation In Blood Vesselsmentioning

confidence: 98%

Redox regulation of cGMP-dependent protein kinase Iα in the cardiovascular system

Prysyazhna

Eaton

2015

Front. Pharmacol.

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“…The vascular endothelium is composed from ECs that are connected to each other via cell junctions; they form a highly dynamic and plastic interface between the blood stream and the interstitial tissue, controlling exchange of water and solutes. EC junctions also play a critical role in regeneration, vasculogenesis and angiogenesis, inflammation and tumor progression (for reviews, see Vestweber, 2012;Fromel and Fleming, 2015;Kazmi et al, 2015;Tesfamariam, 2016;Zou et al, 2016;Filipowska et al, 2017;Godo and Shimokawa, 2017;Szymborska and Gerhardt, 2017;Choi and Moon, 2018;Hida et al, 2018). ECs and EC junctions undergo a specific and different differentiation program in organs and vascular segments (Simionescu et al, 1975(Simionescu et al, , 1976a(Simionescu et al, ,b, 1983Corada et al, 1999;Dejana et al, 2008;Frye et al, 2015;Augustin and Koh, 2017); thus a heterogeneous regulation and dynamics can be assumed (Trepat and Fredberg, 2011).…”

Section: Introductionmentioning

confidence: 99%

Putting VE-cadherin into JAIL for junction remodeling

Cao

Schnittler

2019

Journal of Cell Science

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Junction dynamics of endothelial cells are based on the integration of signal transduction, cytoskeletal remodeling and contraction, which are necessary for the formation and maintenance of monolayer integrity, but also enable repair and regeneration. The VE-cadherincatenin complex forms the molecular basis of the adherence junctions and cooperates closely with actin filaments. Several groups have recently described small actin-driven protrusions at the cell junctions that are controlled by the Arp2/3 complex, contributing to cell junction regulation. We identified these protrusions as the driving force for VE-cadherin dynamics, as they directly induce new VE-cadherin-mediated adhesion sites, and have accordingly referred to these structures as junction-associated intermittent lamellipodia (JAIL). JAIL extend over only a few microns and thus provide the basis for a subcellular regulation of adhesion. The local (subcellular) VE-cadherin concentration and JAIL formation are directly interdependent, which enables autoregulation. Therefore, this mechanism can contribute a subcellularly regulated adaptation of cell contact dynamics, and is therefore of great importance for monolayer integrity and relative cell migration during wound healing and angiogenesis, as well as for inflammatory responses. In this Review, we discuss the mechanisms and functions underlying these actin-driven protrusions and consider their contribution to the dynamic regulation of endothelial cell junctions.

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“…Other mechanisms by which omega-3 PUFA can improve endothelial dysfunction are antioxidation [37], reduction of the vasoconstrictive endothelin-1 (ET-1) [38], and the generation of omega-3 PUFA-derived epoxides from the metabolic pathway of the cytochrome P450 epoxygenases [39]. Recently, Hoshi et al elucidated with an elegant work that DHA can directly induce relaxation of the vascular smooth muscle cells (VSMCs) and acutely reduce blood pressure in anesthetized mice.…”

Section: Omega-3 Pufa In Mechanisms Of Endothelial Dysfunctionmentioning

confidence: 99%

Omega-3 Polyunsaturated Fatty Acids in Blood Pressure Control and Essential Hypertension

Colussi¹,

Catena²,

Novello³

et al. 2016

Update on Essential Hypertension

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Hypertension is a worldwide problem that affects up to % of adults and contributes to the global burden of disability due to cardiovascular disease. Several factors influence blood pressure and participate to the development of hypertension. "mong these factors, polyunsaturated fatty acids of the omega-family omega-PUF" are effective hypotensive agents. Through their anti-inflammatory and antioxidant properties, omega-PUF" can improve cardiac hemodynamics and vascular function and potentially reduce arterial stiffness and atherosclerotic damage. However, despite this promising evidence many meta-analyses on the cardiovascular effect of omega-PUF" were inconclusive. The choice of the omega-PUF" sources, baseline tissue content of these fatty acids, and individual compliance to their intake can be reasons for such a discrepancy between studies. "asic and clinical research on these fatty acids documents interesting mechanisms through which these molecules could be useful in the treatment of hypertension and its related organ damage. The role of the maternal dietary habit during pregnancy and the quality of prenatal growth on the effect of omega-PUF" in cardiovascular system need further investigations. This chapter summarizes the literature of the past years on the antihypertensive effects of this family of essential fatty acids.

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Whatever Happened to the Epoxyeicosatrienoic Acid-Like Endothelium-Derived Hyperpolarizing Factor? The Identification of Novel Classes of Lipid Mediators and Their Role in Vascular Homeostasis

Cited by 21 publications

References 196 publications

Redox regulation of cGMP-dependent protein kinase Iα in the cardiovascular system

Redox regulation of cGMP-dependent protein kinase Iα in the cardiovascular system

Putting VE-cadherin into JAIL for junction remodeling

Omega-3 Polyunsaturated Fatty Acids in Blood Pressure Control and Essential Hypertension

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