Altered expression of pro- and anti-inflammatory cytokines is associated with reduced cardiac function in rats following coronary microembolization

Abstract

Coronary microembolization (CME) is a spontaneous event in patients with ischemic heart disease and a potential iatrogenic complication in patients undergoing coronary interventions. CME induces an obvious inflammatory reaction, characterized by cellular infiltration, particularly of eosinophils, and multifocal microinfarcts. However, little is known on the correlation between pro- and anti-inflammatory cytokines and cardiac function following CME. In this study, microspheres with a diameter of 42 mum were intracoronarily injected into the apex of the left ventricle to induce CME (CME group). Rats injected with normal saline served as controls (sham operated control group). Expression of pro-inflammatory cytokines, TNF-alpha and IL-1beta, and an anti-inflammatory cytokine, IL-10, was measured at 3, 6, 12, 24 h, and 4 weeks post-injection by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. At the same time points, cardiac function and histological changes were evaluated by echocardiographic imagining and H&E staining, respectively. It was observed that the mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-10 all started to increase at 3 h, reached to the peak levels at 12 h, and returned to the normal levels at 4 weeks post-injection. The left ventricular ejection fraction (LVEF) was significantly lower in the CME group than in the control group at 3, 6, 12, 24 h, and 4 weeks post-injection. Obvious myocardial microinfarcts with surrounding myocardial edema and degeneration, caryolysis, and infiltration of neutrophils and monocytes were observed in the CME group at 3, 6, 12, 24 h, and 4 weeks post-injection. Moreover, mRNA expression of TNF-alpha and IL-1beta was negatively correlated with LVEF, although not with myocardial microinfarcts, in the CME group. It is concluded that both protein and mRNA expression of TNF-alpha IL-1beta and IL-10 are dynamically changed following CME, which is associated with reduced cardiac function. Therefore, these cytokines may be potential therapeutic targets for clinical treatment of CME.