Role of canonical transient receptor potential and inflammation in left ventricular fibrosis induced by high salt in Wistar rats

AIM:To explore the role of transient receptor potential channels subfamily C (TRPCs) and inflammation in left ventricular fibrosis induced by high salt and the effect of telmisartan. METHODS:Wistar rats were randomly divided into 3 groups: normal control (C) group (n=13), high salt (8%) model group (HS, n=24) and high salt+telmisartan (T) group (n=12). Tail-cuff artery pressure was determined every 2 weeks. The interstitial collagen deposition and inflammation were observed by Masson and HE staining, respectively. The expression of TRPC1, TRPC3, TRPC6, calcineurin (CaN), nuclear factor-κB p65 (NF-κB p65), transforming growth factor β1 (TGF-β1), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were determined by real-time PCR or Western blotting. RESULTS:Masson staining showed that left ventricle in HS group exhibited severer myocardial interstitial fibrosis compared with C group. TRPC, CaN and NF-κB assays showed that high-salt diet increased the protein expression of TRPC1, TRPC3 and TRPC6, and activated CaN and NF-κB as compared with C group. The results of HE staining, real-time PCR and Western blotting showed that high salt-treated Wistar rats had enhanced cardiac infiltration of inflammatory cells, as well as increased cardiac levels of proinflammatory cytokines (TGF-β1, IL-1β, VCAM-1, ICAM-1 and MCP-1) as compared with C group. After treated with telmisartan, left ventricular mass index and collagen volume fraction became much lower, and the levels of TRPC1, TRPC3, TRPC6, CaN, NF-κB p65, TGF-β1, ICAM-1 and MCP-1 were significantly reduced. CONCLUSION: Inflammation is exacerbated in left ventricular fibrosis induced by high salt. The mechanism may be related to the up-regulation of TRPCs, CaN and NF-κB at mRNA and protein levels. Telmisartan inhibits the expression of TRPCs and NF-κB, and ameliorates the inflammatory responses in left ventricular fibrosis.