NLRP3 and 4 mRNA Expression in Epicardial Adipose Tissue Is Associated to Inflammosome Components Driven by Adipose Tissue Macrophages in Cardiovascular Disease Patients

• Published in: The FASEB journal 2021-05, Vol.35 (S1), p.n/a, Article fasebj.2021.35.S1.01509
• Main Authors: Corsi Romanelli, Massimiliano, Vianello, Elena, Sitzia, Clementina, Dozio, Elena, Tacchini, Lorenza, Kalousová, Marta, Zima, Tomáš
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2021.35.S1.01509

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