The complex P2X<sub>7</sub>receptor/inflammasome in perivascular fat tissue of heavy smokers

Rossi, Chiara; Santini, Eleonora; Chiarugi, Massimo; Salvati, A; Comassi, Mario; Vitolo, Edoardo; Madec, Stéphanie; Solini, Anna

doi:10.1111/eci.12232

Cited by 32 publications

(26 citation statements)

References 39 publications

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“…Interestingly, PV adipocytes (perimesenteric) from smokers, who also exhibit increased oxidative stress, expressed higher levels of MCP-1 mRNA, and enhanced activity of the P2X 7 R-inflammasome complex, as compared with adipocytes isolated from non-smokers. 51 Taken together, these data suggest that adipocytes exhibit considerable plasticity in response to environmental cues, and responsiveness of PV adipocytes to noxious stimuli contained in high fat diet and/or tobacco smoke may promote a pro-inflammatory state conducive to the development of atherosclerosis.…”

Section: Nature Vs Nurture: Adipocyte Plasticitymentioning

confidence: 72%

Proinflammatory Phenotype of Perivascular Adipocytes

Omar

Chatterjee

Tang

et al. 2014

ATVB

140

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Perivascular adipose tissue (PVAT) directly abuts the lamina adventitia of conduit arteries and actively communicates with the vessel wall to regulate vascular function and inflammation. Mounting evidence suggests that the biological activities of PVAT are governed by perivascular (PV) adipocytes, a unique class of adipocyte with distinct molecular and phenotypic characteristics. Perivascular adipocytes surrounding human coronary arteries (pericoronary PV adipocytes) exhibit a reduced state of adipogenic differentiation and a heightened pro-inflammatory state, secreting up to 50-fold higher levels of the pro-inflammatory cytokine MCP-1 as compared with adipocytes from other regional depots. Thus, PV adipocytes may contribute to upregulated inflammation of PVAT observed in atherosclerotic human blood vessels. On the other hand, PV adipocytes also secrete anti-inflammatory molecules such as adiponectin, and elimination of PVAT in rodent models has been shown to augment vascular disease, suggesting that some amount of PVAT is required to maintain vascular homeostasis. Evidence in animal models and in humans suggests that inflammation of PVAT may be modulated by environmental factors, such as high fat diet and tobacco smoke, which are relevant to atherosclerosis. These findings suggest that the inflammatory phenotype of PVAT is diverse depending on species, anatomic location, and environmental factors, and that these differences are fundamentally important in determining a pathogenic versus protective role of PVAT in vascular disease. Further research into the mechanisms that regulate the inflammatory balance of PV adipocytes may yield new insight into, and treatment strategies for, cardiovascular disease.

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Section: Nature Vs Nurture: Adipocyte Plasticitymentioning

confidence: 72%

Proinflammatory Phenotype of Perivascular Adipocytes

Omar

Chatterjee

Tang

et al. 2014

ATVB

140

View full text Add to dashboard Cite

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“…A P2X7 receptor-P2X4 receptor interaction in the process of IL-1β and IL-18 release has been identified in bone marrow-derived dendritic cells [58]. Smoking contributes to the pro-inflammatory status of perivascular visceral adipose tissue by enhancing the expression and activity of the P2X7 receptor-inflammasome complex [59]. Stimulation of P2X7 receptors drives release of both exosomes and microvesicles from several different cell types relevant to inflammation.…”

Section: Inflammation and P2x Receptorsmentioning

confidence: 99%

P2X ion channel receptors and inflammation

Burnstock

2016

Purinergic Signalling

184

153

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Neuroinflammation limits tissue damage in response to pathogens or injury and promotes repair. There are two stages of inflammation, initiation and resolution. P2X receptors are gaining attention in relation to immunology and inflammation. The P2X7 receptor in particular appears to be an essential immunomodulatory receptor, although P2X1 and P2X4 receptors also appear to be involved. ATP released from damaged or infected cells causes inflammation by release of inflammatory cytokines via P2X7 receptors and acts as a danger signal by occupying upregulated P2X receptors on immune cells to increase immune responses. The purinergic involvement in inflammation is being explored for the development of novel therapeutic strategies.

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“…In addition, other CVD risk factors have been demonstrated to have links with PVAT. For example, smoking has been reported to increase the inflammation of PVAT by enhancing the expression and activity of the P2X7R-inflammasome complex, 21 and systemic lupus erythematosus, a known CVD risk factor for women, is associated with greater aortic PVAT and calcification of vascular beds. 22 Clearly, the emerging data from the clinic compels us to develop models to better understand the effects of PVAT in vascular (patho)physiology.…”

Section: Clinical Association Of Pvat With Vascular Diseasesmentioning

confidence: 99%

Perivascular Adipose Tissue in Vascular Function and Disease

Brown

Zhou

Zhang

et al. 2014

ATVB

266

230

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Perivascular adipose tissue (PVAT), long assumed to be nothing more than vessel-supporting connective tissue, is now understood to be an important, active component of the vasculature, with integral roles in vascular health and disease. PVAT is an adipose tissue with similarities to both brown and white adipose tissue, although recent evidence suggests that PVAT develops from its own precursors. Like other adipose tissue depots, PVAT secretes numerous biologically active substances that can act in both autocrine and paracrine fashion. PVAT has also proven to be involved in vascular inflammation. While PVAT can support inflammation during atherosclerosis via macrophage accumulation, emerging evidence suggests that PVAT also has anti-atherosclerotic properties related to its abilities to induce non-shivering thermogenesis and metabolize fatty acids. We here discuss the accumulated knowledge of PVAT biology, and related research on models of hypertension and atherosclerosis.

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The complex P2X₇receptor/inflammasome in perivascular fat tissue of heavy smokers

Abstract: Smoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.

Cited by 32 publications

References 39 publications

Proinflammatory Phenotype of Perivascular Adipocytes

Proinflammatory Phenotype of Perivascular Adipocytes

P2X ion channel receptors and inflammation

Perivascular Adipose Tissue in Vascular Function and Disease

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The complex P2X7receptor/inflammasome in perivascular fat tissue of heavy smokers

Abstract: Smoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.

Cited by 32 publications

References 39 publications

Proinflammatory Phenotype of Perivascular Adipocytes

Proinflammatory Phenotype of Perivascular Adipocytes

P2X ion channel receptors and inflammation

Perivascular Adipose Tissue in Vascular Function and Disease

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Product

Resources

About

The complex P2X₇receptor/inflammasome in perivascular fat tissue of heavy smokers