Expression of NLRP3 in subcutaneous adipose tissue is associated with coronary atherosclerosis.
OBJECTIVE
The promotion of adipose tissue inflammation by lifestyle-related diseases such as obesity and diabetes accelerates atherogenesis; however, the underlying mechanisms remain incompletely understood. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome contributes to chronic inflammation in adipose tissue. Here, we investigated the link between NLRP3 expression in subcutaneous adipose tissue (SAT) and the severity of coronary atherosclerosis.


RESULTS
SAT was obtained from 72 patients who underwent heart device implantation and coronary angiography. Expression of NLRP3 inflammasome-related molecules (NLRP3, IL-1β and IL-18) in SAT were evaluated by quantitative RT-PCR. Laboratory markers related to lifestyle-related diseases were measured. Patients with obesity, dyslipidemia (P < 0.05, respectively), diabetes or hyperuricemia (P < 0.01, respectively) had significantly higher expression of NLRP3. Multivariate analysis demonstrated that body mass index and serum level of uric acid were predictors of NLRP3 expression in SAT. The expression of NLRP3 in SAT correlated negatively with serum adiponectin level (r = -0.23, P < 0.05). Patients with coronary artery disease showed higher NLRP3 expression than patients without significant stenosis (P < 0.01). Furthermore, the expression of NLRP3 in SAT correlated positively with the severity of coronary atherosclerosis as determined by Gensini score (r = 0.47, P < 0.0001) or SYNTAX score (r = 0.55, P < 0.0001). Multiple regression analysis revealed that the expression of NLRP3 in SAT remains as an independent predictors for the severity of coronary atherosclerosis.


CONCLUSIONS
The expression of NLRP3 in SAT, which is affected by lifestyle-related diseases, is associated with the severity of coronary atherosclerosis. Our results suggest that NLRP3 inflammasome in SAT may have a role in atherogenesis.
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Sachiko
S
Bando
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. Electronic address: daiju.fukuda@tokushima-u.ac.jp.
Daiju
D
Fukuda
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Takeshi
T
Soeki
Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Sachiko
S
Nishimoto
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Etsuko
E
Uematsu
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Tomomi
T
Matsuura
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Takayuki
T
Ise
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Takeshi
T
Tobiume
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Koji
K
Yamaguchi
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Shusuke
S
Yagi
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Takashi
T
Iwase
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Hirotsugu
H
Yamada
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Tetsuzo
T
Wakatsuki
Department of Cardio-Diabetes Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Michio
M
Shimabukuro
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Masataka
M
Sata
D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D015415:Biomarkers; D058406:Cardiac Resynchronization Therapy; D002352:Carrier Proteins / Q000378:metabolism*; D003251:Constriction, Pathologic / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000473:pathology; D017147:Defibrillators, Implantable; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D058847:Inflammasomes; D008019:Life Style; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010138:Pacemaker, Artificial; D012307:Risk Factors; D012720:Severity of Illness Index; D050151:Subcutaneous Fat / Q000473:pathology; D014527:Uric Acid / Q000097:blood
D052242:Adiponectin; D015415:Biomarkers; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D014527:Uric Acid
Adipose tissue; Atherosclerosis; Inflammation; Lifestyle-related disease; NLRP3 inflammasome