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Several evidences have suggested that VSMCs apoptosis plays a key role in destabilization and rupture of atherosclerotic plaque. Therefore, protection for VSMCs from apoptosis is a promising approach to stabilize “vulnerable” lesions. However, the mechanisms why VSMCs in fibrous cap often appear as proliferation in early stage but turn to apoptosis in advanced stage are still unknown. Relying on RNA interference (RNAi) technology and calcineurin (CaN) antagonist, the correlation between CaN and RANTES (Regulated on Activated Normal T-Cell Expressed and Secreted) in cultured rat apoptotic VSMCs stimulated by interferon gamma (INFγ 20ng/ml) and CD40 ligand (CD40L 100ng/ml) was investigated in this study. RANTES released from VSMCs in each group was measured by ELISA and its mRNA in VSMCs was determined by Reverse-transcription polymerase chain reaction (RT-PCR). The total activity and expression of CaN in VSMCs were detected by the zymochemistry method and Western blot, respectively. It can be speculated according to the results, elevated CaN concentration in endochylema by CD40-CD40L signal pathway induces VSMCs apoptosis accomplished by the overexpression of RANTES. Therefore, RANTES is a potential treating target for vulnerable atherosclerotic plaque due to its crucial downstream regulating role in the CaN-dependent VSMCs apoptosis.

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doi:10.1042/CBI20090301 Received 9 October 2009/26 January 2010; Accepted 5 February 2010 Published as Immediate Publication 5 February 2010