Birefringent crystals deposition and inflammasome expression in human atheroma plaques by levels of uricemia

Andrés, Mariano; Mendieta, Leticia; Castillo, Elena Argente-Del; Trigueros, M; Miñano, Alberto; Pascual, Eliseo

doi:10.1016/j.jbspin.2022.105423

Cited by 4 publications

(5 citation statements)

References 51 publications

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“…Such vascular deposits could not be later replicated using cadaveric donors who had suffered from gout [78]. Our group found the scattered presence of MSU-looking crystals in peripheral artery specimens using compensated polarized microscopy-although no relationship with patient serum urate levels was established [72]. This suggests that, should these MSU crystals exist in atheroma plaques, their presence might result from the local synthesis that follows increased cell necrosis and turnover, rather than deriving from hyperuricemia.…”

Section: How Msu Crystals May Foster Cardiovascular Risk?mentioning

confidence: 81%

“…Apart from MSU crystal deposits, hyperuricemia itself plays a role in inflammation as well. Soluble urate can enhance the inflammatory response through multiple mechanisms in innate immune cells [71], while increased NLRP3 inflammasome expression has been noted in atheroma plaques from hyperuricemic patients [72].…”

Section: How Msu Crystals May Foster Cardiovascular Risk?mentioning

confidence: 99%

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Gout and Cardiovascular Disease: Mechanisms, Risk Estimations, and the Impact of Therapies

Andrés

2023

GUCDD

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Gout is intimately associated with cardiovascular disease—especially in cases of an atherosclerosis origin, but also with others such as heart failure, atrial fibrillation, or aortic valve stenosis. Besides the common presence of vascular comorbidities in gout sufferers, the disease is—in itself—an independent cardiovascular risk factor, with disease events and mortality attributable to having this condition. This review aims to update the current knowledge regarding several grey areas of the gout–cardiovascular disease spectrum—particularly in terms of risk variations across sex or ancestries, potential monosodium urate crystal deposition in the artery tree as a pathogenic pathway, the efforts undertaken to assess risk estimations in the gout population, and recent controversies surrounding the effects of gout therapies on cardiovascular disease.

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Section: How Msu Crystals May Foster Cardiovascular Risk?mentioning

confidence: 81%

Section: How Msu Crystals May Foster Cardiovascular Risk?mentioning

confidence: 99%

Gout and Cardiovascular Disease: Mechanisms, Risk Estimations, and the Impact of Therapies

Andrés

2023

GUCDD

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“…Furthermore, transgenic mice with platelet-specific ablation of TLR4 and NLRP3 knockout showed improved muscle tissue perfusion after femoral artery ligation [ 215 ]. Hyperuricemia was associated with greater NLRP3 and gasdermin D expression on human atheroma plaques in patients with PAD who were candidates for amputation [ 216 ]. Lastly, human aortic ECs exposed to the plasma from patients with CLTI and treated with simvastatin responded with higher NLRP1 expression than those exposed to plasma from patients with intermittent claudication treated with simvastatin [ 217 ].…”

Section: The Established Role Of Neutrophils In Peripheral Artery Dis...mentioning

confidence: 99%

The Role of Neutrophils in Lower Limb Peripheral Artery Disease: State of the Art and Future Perspectives

Buso

Faggin

Rosenblatt‐Velin

et al. 2023

IJMS

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In recent years, increasing attention has been paid to the role of neutrophils in cardiovascular (CV) disease (CVD) with evidence supporting their role in the initiation, progression, and rupture of atherosclerotic plaque. Although these cells have long been considered as terminally differentiated cells with a relatively limited spectrum of action, recent research has revealed intriguing novel cellular functions, including neutrophil extracellular trap (NET) generation and inflammasome activation, which have been linked to several human diseases, including CVD. While most research to date has focused on the role of neutrophils in coronary artery and cerebrovascular diseases, much less information is available on lower limb peripheral artery disease (PAD). PAD is a widespread condition associated with great morbidity and mortality, though physician and patient awareness of the disease remains low. To date, several studies have produced some evidence on the role of certain biomarkers of neutrophil activation in this clinical setting. However, the etiopathogenetic role of neutrophils, and in particular of some of the newly discovered mechanisms, has yet to be fully elucidated. In the future, complementary assessment of neutrophil activity should improve CV risk stratification and provide personalized treatments to patients with PAD. This review aims to summarize the basic principles and recent advances in the understanding of neutrophil biology, current knowledge about the role of neutrophils in atherosclerosis, as well as available evidence on their role of PAD.

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“…Gout is strongly associated with atherosclerosis and other cardiovascular comorbidities [1,2]. Furthermore, MSU crystals have been reported to deposit in a broad range of extra-articular sites in gout, which include certain cardiac and arterial tissues [3], and in the renal medulla in patients with relatively severe forms of tophaceous gout [4]. Also, case studies of patients with chronic, tophaceous disease have reported MSU crystal deposits in cardiac valves, the myocardium, and the cardiac conducting system [3,[5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…The number of MSU crystals counted significantly correlated with histology-derived intimal thickening and was significantly greater in gout patients compared with non-gout patients [15]. Nonetheless, the robust deposition of basic calcium phosphate (BCP) and cholesterol crystals in atherosclerotic plaques has limited the interpretation of studies using less refined means to evaluate MSU crystal deposits in arterial lesions, such as imaging whole arteries by dual-energy computed tomography (DECT) and performing gross arterial histology [3,10,[16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Atherogenic Activation of Human Vascular Smooth Muscle Cells by Monosodium Urate Crystals

Liu-Bryan,

Guo,

Lee

et al. 2023

GUCDD

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Gout is strongly associated with atherosclerosis and other cardiovascular comorbidities. Furthermore, sites of extra-articular monosodium urate (MSU) crystal deposits in gout can include heart valves and atherosclerotic artery plaques, but with unclear effects therein. Hence, we seminally explored cultured vascular smooth muscle cell (VSMC) responsiveness to MSU crystals. To limit confounding effects, we cultured human aortic VSMCs under serum-free conditions to assess MSU crystal effects on VSMC differentiation and function, differentially expressed genes (DEGs) via RNA sequencing, and selected atherogenic changes in cytokines and the lipidome. MSU crystals induced p38 phosphorylation, IL-6, and VSMC vacuolization with dysregulated autophagy. MSU-crystal-induced DEGs included decreased late-stage autophagosome maturation mediator GABARAPL1, decreased physiologic VSMC differentiation regulators (LMOD1 and SYNPO2), increased ATF4, CHOP, and the intrinsic apoptosis signaling pathway in response to ER stress, and neointimal atherogenic nuclear receptors (NR4A1 and NR4A3). MSU crystals alone increased the levels of cholesterol biosynthetic intermediates 14-demethyl-lanosterol (14-DML), desmosterol, and zymosterol. Adding MSU crystals increased oxidized LDL’s capacity to increase intracellular 27-OH cholesterol, and MSU crystals and oxidized LDL synergistically induced a marked release of arachidonate. In conclusion, MSU crystals deposited in arterial media and neointima have the potential to dysregulate VSMC differentiation and proteostasis, and to induce further atherogenic effects, which include enhanced VSMC loading of oxidized cholesterol intermediates and release of IL-6 and arachidonic acid (AA).

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Birefringent crystals deposition and inflammasome expression in human atheroma plaques by levels of uricemia

Cited by 4 publications

References 51 publications

Gout and Cardiovascular Disease: Mechanisms, Risk Estimations, and the Impact of Therapies

Gout and Cardiovascular Disease: Mechanisms, Risk Estimations, and the Impact of Therapies

The Role of Neutrophils in Lower Limb Peripheral Artery Disease: State of the Art and Future Perspectives

Atherogenic Activation of Human Vascular Smooth Muscle Cells by Monosodium Urate Crystals

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