Hyperuricemia remodels the serum proteome toward a higher inflammatory state

被引：14

作者：

Cabau, Georgiana ^{[1
]}

Gaal, Orsolya ^{[1
,2
]}

Badii, Medeea ^{[1
,2
]}

Nica, Valentin ^{[1
]}

Mirea, Andreea-Manuela ^{[2
]}

Hotea, Ioana ^{[3
]}

Pamfil, Cristina ^{[3
]}

Popp, Radu A. ^{[1
]}

Netea, Mihai G. ^{[2
,4
]}

Rednic, Simona ^{[3
]}

Crisan, Tania O. ^{[1
,2
]}

Joosten, Leo A. B. ^{[1
,2
]}

机构：

[1] Iuliu Hatieganu Univ Med & Pharm, Dept Med Genet, Cluj Napoca, Romania

[2] Radboudumc, Dept Internal Med, Nijmegen, Netherlands

[3] Iuliu Hatieganu Univ Med & Pharm, Dept Rheumatol, Cluj Napoca, Romania

[4] Univ Bonn, Life & Med Sci Inst, Dept Immunol & Metab, Bonn, Germany

来源：

ISCIENCE | 2023年 / 26卷 / 10期

关键词：

URIC-ACID; ASYMPTOMATIC HYPERURICEMIA; OSTEOCLASTIC DIFFERENTIATION; TOPHACEOUS GOUT; HUMAN MONOCYTES; BLOOD-PRESSURE; BONE EROSION; MECHANISMS; EXPRESSION; HYPERTENSION;

D O I：

10.1016/j.isci.2023.107909

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gout is an autoinflammatory disease triggered by a complex innate immune response to MSU crystals and inflammatory triggers. While hyperuricemia is an obligatory risk factor for the development of gout, the majority of individuals with hyperuricemia never develop gout but have an increased risk of developing cardiometabolic disorders. Current management of gout aims at MSU crystal dissolution by lowering serum urate. We apply a targeted proteomic analysis, using Olink inflammation panel, to a large group of individuals with gout, asymptomatic hyperuricemia, and normouricemic controls, and we show a urate-driven inflammatory signature. We add in vivo evidence of persistent immune activation linked to urate exposure and describe immune pathways involved in the pathogenesis of gout. Our results support a pro-inflammatory effect of asymptomatic hyperuricemia and pave the way for new research into targetable mechanisms in gout and cardiometabolic complications of asymptomatic hyperuricemia.

引用

页数：17

共 96 条

[1] Rapid induction of peroxisome proliferator-activated receptor γ expression in human monocytes by monosodium urate monohydrate crystals [J].

Akahoshi, T ;

Namai, R ;

Murakami, Y ;

Watanabe, M ;

Matsui, T ;

Nishimura, A ;

Kitasato, H ;

Kameya, T ;

Kondo, H .

ARTHRITIS AND RHEUMATISM, 2003, 48 (01) :231-239

[2] Silent Monosodium Urate Crystal Deposits Are Associated With Severe Coronary Calcification in Asymptomatic Hyperuricemia An Exploratory Study [J].

Andres, Mariano ;

Quintanilla, Maria-Amparo ;

Sivera, Francisca ;

Sanchez-Paya, Jose ;

Pascual, Eliseo ;

Vela, Paloma ;

Ruiz-Nodar, Juan-Miguel .

ARTHRITIS & RHEUMATOLOGY, 2016, 68 (06) :1531-1539

[3] Human Neutrophils Produce CCL23 in Response to Various TLR-Agonists and TNFα [J].

Arruda-Silva, Fabio ;

Bianchetto-Aguilera, Francisco ;

Gasperini, Sara ;

Polletti, Sara ;

Cosentino, Emanuela ;

Tamassia, Nicola ;

Cassatella, Marco A. .

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2017, 7

[4] Homogenous 96-Plex PEA Immunoassay Exhibiting High Sensitivity, Specificity, and Excellent Scalability [J].

Assarsson, Erika ;

Lundberg, Martin ;

Holmquist, Goeran ;

Bjoerkesten, Johan ;

Thorsen, Stine Bucht ;

Ekman, Daniel ;

Eriksson, Anna ;

Dickens, Emma Rennel ;

Ohlsson, Sandra ;

Edfeldt, Gabriella ;

Andersson, Ann-Catrin ;

Lindstedt, Patrik ;

Stenvang, Jan ;

Gullberg, Mats ;

Fredriksson, Simon .

PLOS ONE, 2014, 9 (04)

[5] Urate-induced epigenetic modifications in myeloid cells [J].

Badii, M. ;

Gaal, O. I. ;

Cleophas, M. C. ;

Kluck, V. ;

Davar, R. ;

Habibi, E. ;

Keating, S. T. ;

Novakovic, B. ;

Helsen, M. M. ;

Dalbeth, N. ;

Stamp, L. K. ;

Macartney-Coxson, D. ;

Phipps-Green, A. J. ;

Stunnenberg, H. G. ;

Dinarello, C. A. ;

Merriman, T. R. ;

Netea, M. G. ;

Crisan, T. O. ;

Joosten, L. A. B. .

ARTHRITIS RESEARCH & THERAPY, 2021, 23 (01)

[6] Pro-Aging Effects of Xanthine Oxidoreductase Products [J].

Battelli, Maria Giulia ;

Bortolotti, Massimo ;

Bolognesi, Andrea ;

Polito, Letizia .

ANTIOXIDANTS, 2020, 9 (09) :1-16

[7] Treatment with Statins Does Not Revert Trained Immunity in Patients with Familial Hypercholesterolemia [J].

Bekkering, Siroon ;

Stiekema, Lotte C. A. ;

Moens, Sophie Bernelot ;

Verweij, Simone L. ;

Novakovic, Boris ;

Prange, Koen ;

Versloot, Miranda ;

van Lennep, Jeanine E. Roeters ;

Stunnenberg, Henk ;

de Winther, Menno ;

Stroes, Erik S. G. ;

Joosten, Leo A. B. ;

Netea, Mihai G. ;

Riksen, Niels P. .

CELL METABOLISM, 2019, 30 (01) :1-2

[8]

Berse B, 1999, CLIN EXP IMMUNOL, V115, P176

[9] Cutting Edge: FAS (CD95) Mediates Noncanonical IL-1β and IL-18 Maturation via Caspase-8 in an RIP3-Independent Manner [J].

Bossaller, Lukas ;

Chiang, Ping-I ;

Schmidt-Lauber, Christian ;

Ganesan, Sandhya ;

Kaiser, William J. ;

Rathinam, Vijay A. K. ;

Mocarski, Edward S. ;

Subramanian, Deepa ;

Green, Douglas R. ;

Silverman, Neal ;

Fitzgerald, Katherine A. ;

Marshak-Rothstein, Ann ;

Latz, Eicke .

JOURNAL OF IMMUNOLOGY, 2012, 189 (12) :5508-5512

[10] Urate-induced immune programming: Consequences for gouty arthritis and hyperuricemia [J].

C'abau, Georgiana ;

Crisan, Tania O. ;

Kluck, Viola ;

Popp, Radu A. ;

Joosten, Leo A. B. .

IMMUNOLOGICAL REVIEWS, 2020, 294 (01) :92-105

← 1 2 3 4 5 6 7 8 9 10 →