Inflammation Activation Contributes to Adipokine Imbalance in Patients with Acute Coronary Syndrome

Abstract

Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS) for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1) control group; (2) SA (stable angina) group; and (3) ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day) and high-statin (atorvastatin, 20 mg/kg/day) group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.

Fig 1. Effects of atorvastatin on resistin and adiponectin in AMI mice.

(A) As compared with sham group, resistin expressions in adipose tissue were increased in all AMI mice. However, pre-treatment of atorvastatin dose-dependently attenuated AMI-induced up-regulation of resistin in mice. (B) Adiponectin expressions were markedly lower in all AMI mice than those in sham group. In contrast, administration of atorvastatin dose-dependently increased AMI-induced down- regulation of adiponectin in mice. *P < 0.05, **P < 0.01, ***P < 0.001 vs. control; # P < 0.01 vs. AMI; § P < 0.05 vs. low-statin group.

Fig 2. Effects of atorvastatin on resistin and adiponectin in cells.

(A) Treatment with ox-LDL increased resistin expressions in mouse 3T3-L1 adipocytes. However, atorvastatin dose- dependently attenuated ox-LDL-induced elevation of resistin in adipocytes. (B) Ox-LDL treatment remarkably reduced adipocyte adiponectin expressions, but addition of atorvastatin dose-dependently ameliorated ox-LDL-induced reduction of adiponectin. (C) Treated with ox-LDL, resistin expressions were significantly increased in human macrophages. However, administration of atorvastatin dose-dependently reversed ox-LDL-induced up-regulation of resistin. *P < 0.05, **P < 0.01, ***P < 0.001 vs. Control; # P < 0.01 vs. ox-LDL group; § P < 0.05 vs. low-statin group.