RETRACTED: Agonism of GPR120 prevents ox-LDL-induced attachment of monocytes to endothelial cells

Jiang, Tiechao; Jiang, Dongli; You, Dong; Zhang, Lirong; Liu, Long; Zhao, Qini

doi:10.1016/j.cbi.2019.108916

Cited by 16 publications

(9 citation statements)

References 43 publications

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“…Additional evidence suggests that GPR120, a GPCR for omega-3 fatty acid, seems to counteract oxidized-LDL/P2Y2-mediated inflammation in atherosclerosis, inhibiting the binding of monocytes to ECs [ 83 ]. GPR120 is downregulated by exposure to oxidized-LDL, suggesting a role for GPR120 in mediating oxidized-LDL insult.…”

Section: P2y Receptor Signaling and Endothelial Dysfunctionmentioning

confidence: 99%

P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases

Strassheim

Verin

Bátori

et al. 2020

IJMS

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Purinergic G-protein-coupled receptors are ancient and the most abundant group of G-protein-coupled receptors (GPCRs). The wide distribution of purinergic receptors in the cardiovascular system, together with the expression of multiple receptor subtypes in endothelial cells (ECs) and other vascular cells demonstrates the physiological importance of the purinergic signaling system in the regulation of the cardiovascular system. This review discusses the contribution of purinergic P2Y receptors to endothelial dysfunction (ED) in numerous cardiovascular diseases (CVDs). Endothelial dysfunction can be defined as a shift from a “calm” or non-activated state, characterized by low permeability, anti-thrombotic, and anti-inflammatory properties, to a “activated” state, characterized by vasoconstriction and increased permeability, pro-thrombotic, and pro-inflammatory properties. This state of ED is observed in many diseases, including atherosclerosis, diabetes, hypertension, metabolic syndrome, sepsis, and pulmonary hypertension. Herein, we review the recent advances in P2Y receptor physiology and emphasize some of their unique signaling features in pulmonary endothelial cells.

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Section: P2y Receptor Signaling and Endothelial Dysfunctionmentioning

confidence: 99%

P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases

Strassheim

Verin

Bátori

et al. 2020

IJMS

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“…According to current paradigm, atherosclerosis is a systemic low-grade inflammatory disease characterized by progressive changes in arterial walls that involve many types of cells [ 1 , 2 ]. Dysfunction of endothelial cells, phenotypic changes of vascular smooth muscle cells (VSMC), as well as inflammatory stimulation and infiltration of lymphocytes and monocytes into the vessel wall were all reported to contribute to atherogenesis and formation of atherosclerotic plaques [ 1 , 3 ]. Studies in atherosclerosis underline a complex role of macrophages in local modulation of inflammation, development of plaques, and their rupture [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Anti-Atherosclerotic Action of FFAR4 Agonist TUG-891 in ApoE–Knockout Mice Is Associated with Increased Macrophage Polarization towards M2 Phenotype

Stachyra

Wiśniewska

Kuś

et al. 2021

IJMS

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Background: Over the past few years, a better understanding of the biology of G-protein coupled receptors (GPRs) has led to the identification of several receptors as novel targets for free fatty acids (FFAs). FFAR4 has received special attention in the context of chronic inflammatory diseases, including atherosclerosis, obesity and NAFLD, through to its anti-inflammatory effect. Methods: The present study investigates the influence of prolonged treatment with TUG-891-FFAR4 agonist on the development of atherosclerosis plaque in apoE–knockout mice, using morphometric and molecular methods. Results: TUG-891 administration has led to the reduction of atherosclerotic plaque size and necrotic cores in an apoE–knockout mice model. TUG-891-treated mice were administered subcutaneously at a dose of 20 mg/kg three times a week for 4 months. The FFAR4 agonist reduced the content of pro-inflammatory M1-like macrophages content in atherosclerotic plaques, as evidenced by immunohistochemical phenotyping and molecular methods. In atherosclerotic plaque, the population of smooth muscle cells increased as evidenced by α-SMA staining. We observed changes in G-CSF and eotaxin markers in the plasma of mice; changes in the levels of these markers in the blood may be related to macrophage differentiation. Importantly, we observed a significant increase in M2-like macrophage cells in atherosclerotic plaque and peritoneum. Conclusions: Prolonged administration of TUG-891 resulted in significant amelioration of atherogenesis, providing evidence that the strategy based on macrophage phenotype switching toward an M2-like activation state via stimulation of FFAR4 receptor holds promise for a new approach in the prevention or treatment of atherosclerosis.

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“…Atherosclerosis is an inflammatory disease that involves many types of cells [ 23 , 24 ]. Dysfunction of endothelial cells, phenotypic changes of vascular smooth muscle cells (VSMC), as well as inflammatory stimulation and monocyte infiltration into the vessel wall all were reported to contribute in concert to atherogenesis [ 23 , 25 ]. Several metabolic diseases like diabetes and obesity—known risk factors of atherosclerosis—can lead to an increased level of FFA, which in turn can aggravate cell activation and inflammation.…”

Section: Ffas and Atherosclerosismentioning

confidence: 99%

“…Recently, Jiang et al demonstrated that GW9508 and TUG- 891 reduced oxidative stress in cultured human aortic endothelial cells (HAECs) via inhibition of the production of ROS and NOX-4, as well as downregulated the expression of VCAM-1 and E-selectin. The latter was associated with a decreased number of THP-1 monocytes attached to HAECs [ 25 ]. These results seem to be in agreement with older observations, that DHA (which is a known activator of FFAR4) could inhibit expression of adhesion molecules (ICAM-1, VCAM-1) in TNF-α-induced HUVECs [ 31 ].…”

Section: Ffar4 and Atherosclerosismentioning

confidence: 99%

“…Moreover, it was shown that the overexpression of KLF4 in endothelial cells induces the expression of multiple anti-inflammatory and anti-thrombotic factors including endothelial nitric-oxide synthase and thrombomodulin, whereas its knockdown enhances TNF-α-induced VCAM-1 expression [ 34 ]. Interestingly, FFAR4 agonists showed the ability to reverse downregulation of KLF4 and induction of adhesion molecules in HAECs [ 25 ].…”

Section: Ffar4 and Atherosclerosismentioning

confidence: 99%

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Anti-Atherosclerotic Potential of Free Fatty Acid Receptor 4 (FFAR4)

Stachyra

Olszanecki

2021

Biomedicines

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Fatty acids (FAs) are considered not only as a basic nutrient, but are also recognized as signaling molecules acting on various types of receptors. The receptors activated by FAs include the family of rhodopsin-like receptors: GPR40 (FFAR1), GPR41 (FFAR3), GPR43 (FFAR2), GPR120 (FFAR4), and several other, less characterized G-protein coupled receptors (GPR84, GPR109A, GPR170, GPR31, GPR132, GPR119, and Olfr78). The ubiquitously distributed FFAR4 can be activated by saturated and unsaturated medium- and long-chain fatty acids (MCFAs and LCFAs), as well as by several synthetic agonists (e.g., TUG-891). The stimulation of FFAR4 using selective synthetic agonists proved to be promising strategy of reduction of inflammatory reactions in various tissues. In this paper, we summarize the evidence showing the mechanisms of the potential beneficial effects of FFAR4 stimulation in atherosclerosis. Based partly on our own results, we also suggest that an important mechanism of such activity may be the modulatory influence of FFAR4 on the phenotype of macrophage involved in atherogenesis.

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RETRACTED: Agonism of GPR120 prevents ox-LDL-induced attachment of monocytes to endothelial cells

Cited by 16 publications

References 43 publications

P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases

P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases

The Anti-Atherosclerotic Action of FFAR4 Agonist TUG-891 in ApoE–Knockout Mice Is Associated with Increased Macrophage Polarization towards M2 Phenotype

Anti-Atherosclerotic Potential of Free Fatty Acid Receptor 4 (FFAR4)

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