Inflammasome activation by NLRP1 and NLRC4 in patients with coronary stenosis

Objective and design: We performed an experimental, analytical and prospective study to evaluate the systemic activation of inflammasome in atherosclerosis' patients, in order to shed light into responsible mechanisms for plaque formation. Subjects: We included sixty individuals distributed into 3 groups: 2 groups based on the report from the angiography (severe lesions - SL and primary lesions - PL) and 1 group enclosing healthy individuals (HC). Methods: The expression assays of inflammasome genes NLRP1, NLRC4, GASP-1 and IL-1 beta were performed using Real Time qPCR, with specific Taqman Assays. IL-1 beta serum levels were analysed by commercial kit. Were applied the Shapiro-Wilk and Student's T-test as statistical tests. Statistical significance was set to p <= 0.05. Results: Upregulation of NLRP1 (+ 3.47 FC, p = 0.0001), NLRC4 (+7.06 FC, p = 6.792 x 10(-09)) and IL-1 beta (+ 2.43 FC, p = 0.005) was observed in all atherosclerosis patients when compared to HC. According to stenosis severity, patients with primary lesions showed upregulation of inflammasome genes NLRP1 (+ 2.87 FC, p = 0.0008), NLRC4 (+ 6.34 FC, p = 4.134 x 10(-07)) and IL-1 beta (+ 3.39 FC, p = 0.0012) with respect to the HC group. No statistical difference was found in IL-1 beta serum levels according the assessed groups. Conclusions: Inflammasome activation in atherosclerosis's patients can be systemic altered and may be triggered by NLRP1 and NLRC4 receptors. IL-1 beta gene expression was identified in our study as an important systemic detectable marker of plaque severity.