Inflammasome activation by NLRP1 and NLRC4 in patients with coronary stenosis

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.

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).

The expression assays of inflammasome genes NLRP1, NLRC4, CASP-1 and IL-1β were performed using Real Time qPCR, with specific Taqman Assays. IL-1β 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.

Upregulation of NLRP1 (+3.47 FC, p = 0.0001), NLRC4 (+7.06 FC, p = 6.792 × 10^-09) and IL-1β (+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 × 10^-07) and IL-1β (+3.39 FC, p = 0.0012) with respect to the HC group. No statistical difference was found in IL-1β serum levels according the assessed groups.

Inflammasome activation in atherosclerosis's patients can be systemic altered and may be triggered by NLRP1 and NLRC4 receptors. IL-1β gene expression was identified in our study as an important systemic detectable marker of plaque severity.