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To investigate the role of CREG in the process of cardiac inflammation and remodeling induced by high salt in salt sensitive hypertensive rats.
Sixty-four Dahl salt sensitive (Dahl-SS) rats were randomly divided into normal salt (NS, 0.3% NaCl) and high salt (HS, 8% NaCl) group. Blood pressure was measured by tail-cuff method every week. Masson trichrome staining was used to evaluate cardiac fibrosis deposition. Immunohistochemical staining was used to detecting the expression of macrophage in the myocardium after NS and HS intake at 6 week and 8 week. Hearts were harvested and the expression of CREG in heart tissues was detected by Western blot at 2 week, 4 week, 6 week and 8 week after NS and HS intake. Microarray analysis of CREG-/- mouse cardiac tissue revealed that S100A8/A9 were highly upregulated. Immunoprecipitation (IP) method was used to detect the interaction between CREG and S100A8/A9. Cardiofibroblasts (CFs) with CREG overexpression or knocked down were established by using AdCREG and siCREG respectively. Then macrophage infiltration was detected by Transwell method in CFs to evaluated CREG’s effects.
Compared with the NS group, the blood pressure increased significantly in Dahl-SS rats after 1 week of HS intake. At 8 weeks, the high salt rats appeared obvious fibrosis reconstruction and macrophage infiltration. HS intake significantly reduced the myocardial CREG expression in Dahl-SS rats at 4 weeks. IP found that CREG interacted with S100A8/A9. AdCREG fibroblasts inhibited macrophage infiltration.
CREG ameliorated myocardial fibrosis in Dahl rats by inhibiting S100A8/9 mediated microphage infiltration.