Elevated levels of triglycerides and vldl-cholesterol provoke activation of nlrp1 inflammasome in endothelial cells.

International journal of cardiology

PubMedID: 27372042

Bleda S, De Haro J, Varela C, Ferruelo A, Acin F. Elevated levels of triglycerides and vldl-cholesterol provoke activation of nlrp1 inflammasome in endothelial cells. Int J Cardiol. 2016;22052-55.
BACKGROUND
Soluble stimuli present in the plasma of patients with peripheral arterial disease (PAD) are capable of directly stimulating intracellular signalling in endothelium. Oxidized-LDL (oxLDL) induces NLRP3 inflammasome activation in macrophages. However, it is not clear how lipid profile affect NLRP1 inflammasome gene expression in endothelial cells. In this study, the effect of cholesterol and TG of plasma of patients with PAD on NLRP1 inflammasome gene expression in human arterial endothelial cells (HAECS) was assessed.

METHODS
We included 113 patients with symptomatic PAD. HAECs were stimulated for 2h using the plasma samples of the study participants. The NLRP1 quantification of the transcription was carried out on the 7500 real-time PCR system using the Taqman® Universal PCR Master Mix and Assays on demand. Relative quantification of the NLRP1 expression was carried out using the ??Ct (threshold cycle) comparative method.

RESULTS
Plasma from patients with elevated VLDL-cholesterol levels (>33.6mg/dL, the median value of the sample) provoked a higher expression of NLRP1 inflammasome in HAECs (RQ=1.15±0.23 vs. 1.05±0.69; p=0.045), as well as plasma from patients with elevated TGs levels (>168mg/dL, the median value of the sample) (RQ=1.15±0.23 vs. 1.05±0.69; p=0.045). A positive correlation was found between NLRP1 inflammasome expression and VLDL-cholesterol plasma levels (r=0.4; p<0.001) as between NLRP1 inflammasome expression and TG levels (r=0.4; p<0.001).

CONCLUSIONS
Plasma TG and VLDL cholesterol of patients with atherosclerosis, manifested as PAD, promote the in vitro NLRP1 inflammasome expression in HAECs.