NLRC5 in Macrophages Promotes Atherosclerosis in Acute Coronary Syndrome by Regulating STAT3 Expression

The mortality rate of cardiovascular and cerebrovascular diseases ranks first among all causes. This study elucidated the role and potential mechanism of the NLRC5 gene in atherosclerosis (AS). We enrolled patients (number = 30) diagnosed with AS and healthy volunteers (number = 30) as controls from our hospital. In patients with AS, the levels of serum NLRC5 were up-regulated (Fig. 1A) and positively correlated with CIMT/CRP. In a mouse model of AS, the expression of serum NLRC5 mRNA was increased at 6 or 12 weeks after inducing AS. The expression of NLRC5 protein was found to be elevated in a mouse model of AS. The inhibition of NLRC5 reduced development of AS in ApoE^-/- Mice. Reducing NLRC5 inhibited the polarization of M2 macrophages and shifted macrophages towards proinflammatory M1 phenotype. STAT3 was identified as a target of NLRC5, with NLRC5 protein expression shown to reduce STAT3 ubiquitination. Methylation promoted NLRC5 DNA stability in vitro model of AS. Sh-NLRC5 increased M1/M2 macrophage ratio, foam cell formation and ox-LDL uptake. STAT3 reduced the effects of sh-NLRC5-mediated M1/M2 macrophage ratio in model of AS. These data confirmed that NLRC5 in macrophages promotes atherosclerosis in acute coronary syndrome by regulating STAT3 expression. This suggests that NLRC5 could be a potential target for the treatment of premature AS.