Nitrate esters alleviated coronary atherosclerosis via inhibition of NF-κB-regulated macrophage polarization shift in epicardial adipose tissue

Nitrate esters have been used in clinical practice for more than one century for the treatment of angina. Their clinical effectiveness is due to vasodilator activity in arteries through a method of delivering nitric oxide (NO), or a NO-like compound. Recently, an increasing numbers of functions of this molecule in biology and pathophysiology have been discovered. Macrophage polarization shift in epicardial adipose tissue (EAT) has been demonstrated to be correlated with the severity of coronary artery disease (CAD). In this study, we aimed to investigate whether nitrate esters could improve coronary atherosclerosis via inhibition of macrophage polarization shift in EAT. A case-control study enrolled 48 subjects in two groups: CAD patients with or without nitrate esters treatment. Infiltration of M1/M2 macrophages and the expressions of pro- and anti-inflammatory cytokines in EAT and subcutaneous white adipose tissue (SWAT) were investigated by immunohistochemical stain among subjects undergoing coronary artery bypass graft surgery. The expression levels of metabolic genes were investigated by real-time PCR. We found that nitrate esters treatment significantly inhibited NF-small ka, CyrillicB activity and decreased macrophages infiltration and M1/M2 macrophages ratio in EAT in CAD patients. The expressions of pro-inflammatory cytokines were significantly decreased, along with significantly elevated expressions of anti-inflammatory cytokines in CAD patients with nitrate esters treatment, corresponding EAT dysfunction was ameliorated and the severity of CAD patients (Gensini score) was significantly decreased. The protective effects on macrophage polarization and EAT function via NF-small ka, CyrillicB activity inhibition suggested a potential mechanism of nitrate esters in alleviating the severity of CAD.