Lipocalin 2-induced myocardial collagen fibril deposition participates in Kawasaki disease-related myocardial injury

  AIM  To investigate whether lipocalin 2-induced myocardial collagen fibril deposition and inflammatory reactions participated in Kawasaki disease-related myocardial injury using the rat model of Kawasaki disease established by lactobacillus casei cell wall extract (LCWE).

  METHODS  Forty rats (1 month old) were randomly divided into control group and LCWE model group. In LCWE model group, LCWE was injected intraperitoneally to established Kawasaki disease rat model. ELISA was used to detect the plasma Lcn 2 levels in plasma and cardiac tissue homogenates of Kawasaki disease rats, cardiac ultrasound was used to detect systolic and diastolic functions in rats and Masson staining was used to evaluate the degree of myocardial fibrosis. The expressions of IL-6, CD3, CD45 and Collagen I mRNA in myocardial tissue were detected by real-time fluorescence quantitative PCR and the expressions of Collagen I P, NF-кB, and IкB were detected by Western blotting.

  RESULTS  Echocardiography confirmed that the left ventricular end-diastolic dimension (LVIDd) and left ventricular ejection fraction (LVEF) were decreased in Kawasaki disease rats compared with those in control group (P<0.05). Masson staining showed a certain degree of myocardial fibrosis and collagen deposition in Kawasaki disease rats. The mRNA expression levels of inflammation-related molecules, such as IL-6, CD3 and CD45, in the myocardium were significantly elevated (P<0.05). The cardiac tissue and circulation levels of Lcn 2 in Kawasaki disease rats were significantly higher than those in control group (P<0.05). More importantly, the cultured cardiac fibroblasts were treated with Lcn 2 (10 ng/ml) for 48 hours and then the mRNA and protein expression levels of Collagen I of the cultured cardiac fibroblasts were significantly increased (P<0.05) and the phosphorylation of NF-кB and IκB in cardiac fibroblasts was significantly up-regulated (P<0.05). Treatment with IκB inhibitor BAY 11-7082 (2.5 μmol/L) effectively inhibited Lcn 2 up-regulation of Collagen I protein.

  CONCLUSION  Lcn 2-induces myocardial collagen fibril deposition and inflammatory reactions by activating the NF-кB signal participates in Kawasaki disease-related myocardial injury.