Polysaccharides from chayote enhance lipid efflux and regulate NLRP3 inflammasome priming in macrophage-like THP-1 cells exposed to cholesterol crystals

Background: Despite the advances of current optimal treatment of atherosclerotic disease, the incidence of events after acute coronary syndrome (ACS) remains high. Colchicine, with its well-established pleiotropic anti-inflam- matory effects, may inhibit NLRP3 inflammasome, a key mediator in atherosclerosis-associated inflammation (AAI) thus reducing systemic inflammation. NRLP3 inflammasome activation inside leukocytes (mainly monocytes and neutrophils) is precipitated by cholesterol crystals that are present in all atherosclerosis stages. 􏰟􏰋􏰡􏰈􏰇􏱎􏰋􏰇􏰆􏰂 􏰍􏰀􏰂􏰅􏰩􏰍􏰂􏰅􏰃􏰆 􏰃􏰜 􏰢􏰎􏰃􏰐􏰅􏰆􏰜􏰏􏰍􏰝􏰝􏰍􏰂􏰃􏰎􏰁 􏰀􏰁􏰂􏰃􏰄􏰅􏰆􏰇􏰈 􏰈􏰋􏰀􏰌 􏰍􏰈 􏰅􏰆􏰂􏰇􏰎􏰏􏰇􏰋􏰄􏰅􏰆􏰐􏰑􏰒 􏰍􏰆􏰗 􏰅􏰆􏰂􏰇􏰎􏰏􏰇􏰋􏰄􏰅􏰆􏰐􏰑􏰣 􏰳􏰅􏰏􏰏 􏰜􏰃􏰏􏰏􏰃􏰳􏰨 􏰘􏰌􏰇􏰈􏰇 cytokines are the crucial inflammatory pathway mediators that promote the formation of plaque and instability in the inflammatory cascade. Objective: This review will elaborate on the function of immune cells in atherosclerosis, explain the mechanisms of NLRP3 inflammasome activation in the context of AAI, and address the possible role of colchicine specifically targeting NLRP3 inflammasome and its concomitant downstream mediators in ACS, and provide an overview of current or ongoing studies produced in this area. Discussion : NRLP3 inflammasome activation inside leukocytes (mainly monocytes and neutrophils) is precipitat- ed by cholesterol crystals that are present in all atherosclerosis stages. Subsequent activation of pro-inflammatory pathway mediators that promote the formation of plaque and instability in the inflammatory cascade. A potential advantage of a medication acting through an inflammatory milieu found in atherosclerotic lesions has recently become the need for novel therapeutic options. Colchicine, with its well-established pleiotropic anti-inflammato- ry effects, may inhibit NLRP3 inflammasome, a key mediator in atherosclerosis-associated inflammation (AAI) thus reducing systemic inflammation. Conclusion: Colchicine is a safe and reliable medication for ACS patients, alongside reveal various benefit in reducing inflammation through inhibition of NLRP3 Inflammasome`

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Cholesterol crystals activate the NLRP3 inflammasome in human monocytes and macrophages

Chemistry and Physics of Lipids ◽

10.1016/j.chemphyslip.2010.05.084 ◽

2010 ◽

Vol 163 ◽

pp. S27-S28 ◽

Cited By ~ 1

Author(s):

K. Rajamäki ◽

J. Lappalainen ◽

K. Öörni ◽

E. Välimäki ◽

S. Matikainen ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Human Monocytes ◽

Cholesterol Crystals ◽

Monocytes And Macrophages ◽

Human Monocytes And Macrophages

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Colchicine Alleviates Cholesterol Crystal-Induced Endothelial Cell Pyroptosis through Activating AMPK/SIRT1 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9173530 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18 ◽

Cited By ~ 2

Author(s):

Mengyue Yang ◽

Hang Lv ◽

Qi Liu ◽

Lu Zhang ◽

Ruoxi Zhang ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Cardiovascular Diseases ◽

Nlrp3 Inflammasome ◽

Cell Injury ◽

Inflammatory Factors ◽

Acute Gout ◽

Cholesterol Crystal ◽

Cholesterol Crystals ◽

Related Proteins

Cholesterol crystal- (CC-) induced endothelial cell inflammation and pyroptosis play an important role in the development of cardiovascular diseases, especially in atherosclerosis (AS). Increasing evidence suggests that cholesterol crystals are known to be a pivotal pathological marker of atherosclerotic plaque vulnerability. As a classical nonspecific anti-inflammatory drug, colchicine has been widely used in the treatment of acute gout. However, whether colchicine could alleviate CC-induced endothelial cell injury and the related mechanisms remains to be addressed. In this study, the protective effect of colchicine on human umbilical vein endothelial cells (HUVECs) was confirmed. Our results revealed that after cotreatment with colchicine and cholesterol crystals in endothelial cells, the uptake of cholesterol crystals was significantly decreased, the cell viability was obviously increased, and the release of lactate dehydrogenase (LDH) and the number of pyroptotic cells decreased significantly; then, the expression of NLRP3 inflammasome-related proteins and various inflammatory factors was also visibly suppressed; moreover, as a potent activator of NLRP3 inflammasome, the intracellular ROS level was clearly reduced, while mitochondrial membrane potential improved significantly. In addition, the expression levels of AMP-dependent kinase (AMPK) pathway-related proteins as well as various antioxidant enzymes were elevated notably in varying degrees. However, the above effects of colchicine were completely offset by the treatment of siRNA targeting AMPKα and Sirtuin1 (SIRT1). Therefore, we conclude that colchicine plays a crucial role in alleviating the intracellular inflammatory response and NLRP3 inflammation activation, attenuating the levels of cellular oxidative stress and pyroptosis in endothelial cells via regulating AMPK/SIRT1 signaling, which may be a concrete mechanism for the secondary prevention of cardiovascular diseases.

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Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

Clinical Science ◽

10.1042/cs20191213 ◽

2020 ◽

Vol 134 (17) ◽

pp. 2243-2262

Author(s):

Danlin Liu ◽

Gavin Richardson ◽

Fehmi M. Benli ◽

Catherine Park ◽

João V. de Souza ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Molecular Targets ◽

Therapeutic Interventions ◽

Low Grade ◽

Cardiovascular Research ◽

Inflammatory Processes ◽

Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

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