Premium
NLRP3 and 4 mRNA Expression in Epicardial Adipose Tissue Is Associated to Inflammosome Components Driven by Adipose Tissue Macrophages in Cardiovascular Disease Patients
Author(s) -
Corsi Romanelli Massimiliano,
Vianello Elena,
Sitzia Clementina,
Dozio Elena,
Tacchini Lorenza,
Kalousová Marta,
Zima Tomáš
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01509
Subject(s) - adipose tissue , inflammation , medicine , overweight , adipose tissue macrophages , endocrinology , obesity , receptor , pathology , white adipose tissue
Visceral obesity is characterized by low grade chronic inflammation especially driven by activated adipose tissue macrophages (ATMs) infiltration in response to danger‐associated molecular patterns (DAMPs) including necrotic adipocytes and pro‐inflammatory fat mediators. Among pattern recognition receptors (PPRs), nucleotide‐binding and oligomerization domain (NOD)‐like receptors (NLRs) gained attention as part of inflammasomes of adipose tissue which can promote insuline resistance and amplify inflammation through ATMs activation in fat tissue. Nod‐like receptor protein 3 and 4 inflammasomes have been extensively studied in adipose tissue but is unclear their role in a peculiar visceral fat depot known as epicardial adipose tissue (EAT) contiguous to the myocardium and directly involved in cardiac inflammation and outcomes. In this study we evaluated NLR 3 and 4 protein (NLRP3 and 4) expression in EAT and their association to local inflammosomes and ATMs activation in overweight cardiovascular disease (CVDs) patients. We enrolled at IRCCS Policlinico San Donato 33 CVDs patients who underwent to open heart surgery and their EAT thickness, anthropometric and biochemical data were measured. Blood, plasma and EAT biopsies were collected for molecular and proteomic assays. All patients given their informed consent according to the Basic Principles of the Declaration of Helsinki and their extension . Our data shown that NLRP3 and 4 mRNA were expressed in EAT of overweight CVDs patients. NLRP4 mRNA expression increased during fat mass gain, indeed its expression correlates with EAT measurement (r=0.53, p=0.02), body mass index (0.41, p=0.01), weight (r=0.35, p=0.04) and waist (r=0.36, p=0.03). Notably both NLRP3 and 4 mRNA expression in EAT correlate with the major inflammasome genes associated to ATMs activation including ITGAX encoding for CD11c (isoform 3 r=0.38, p=0.02; isoform 4 r=‐0.46, p=0.006), MRC1 encoding for CD206 (isoform 3 r=0.68, p=0.0001; isoform 4 r=‐0.48, p=0.004), CCL2 encoding for MCP1(isoform 3 r=0.39, p=0.02; isoform 4 not statistically significant). Interesting the two isoforms shown a direct association to TNF‐α expression in EAT (p<0.001 for both NLRPs), suggesting their implication in ATMs activation and the promotion of local inflammation in this visceral depot. In conclusion our results demonstrated that NLRP3 and 4 were expressed in EAT of overweight CVD patients and NLRP4 expression increases during fat mass increase. Moreover, both NLRPs isoforms are associated to the local activation ATMs inflammasomes which could be potentially implicated to cardiovascular outcomes in overweight CVDs population.