Nlrc4 Inflammasome Expression After Acute Myocardial Infarction in Rats

Abstract

Acute myocardial necrosis activates the immune response and inflammatory processes. Although the initial response is helpful in restoring tissue injury, dysregulated and exacerbated inflammation contributes to the progression of cardiac remodeling. Inflammasomes play important roles in post-infarction inflammation. NALP1/NLRP1, NLRP 3, and NLRC4 are the best-known inflammasomes. NLRP3, which has received the most study in cardiovascular disease, has been linked to increased IL-1β (IL1B) production and caspase-1 activity, as well as impaired cardiac function. The role of NLRP1 and NLRC4 inflammasomes after acute myocardial infarction (MI) is poorly understood. We evaluated the expression of myocardial inflammasomes and inflammatory markers 72 h after MI in rats. Male Wistar rats were divided into Sham (n = 15) and MI (n = 16) groups. MI was induced by ligating the left anterior descending coronary artery. Infarct size was assessed by histology. Myocardial protein and gene expression was analyzed by Western blot and RT-qPCR, respectively. IL-1β (Il1b) concentrations in serum and heart macerate supernatant were evaluated by ELISA. Statistical analysis was performed using Student's <i>t</i> test. Rats with an MI size less than 30% of the total left ventricle (LV) area were excluded; infarct size was 46 ± 11% of the total LV area in MI. The interstitial collagen fraction was higher in MI. Nlrc4, caspase-1 (Casp1), and IL-1β (Il1b) protein expressions were higher in MI. Nlrp3, Nlrp1, ASC (Pycard), pro-caspase-1, and pro-IL-1β (Il1b) expressions did not differ between groups. Expression of the Nlrp3 and ASC (Pycard) genes, as well as myocardial and serum IL-1β (Il1b) concentrations, was higher in MI. Acute post-myocardial infarction inflammation is characterized by increased protein expression of Nlrc4, caspase-1, and interleukin-1β; increased gene expression of Nlrp3 and ASC (Pycard); and elevated serum and myocardial concentrations of interleukin-1β in combination with an increased myocardial collagen interstitial fraction.