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Atorvastatin induces VSMCs apoptosis in a dose- and time-dependent manner. Transfection of survivin ASODN can directly induce VSMCs apoptosis. The mechanisms of VSMCs apoptosis induced by atorvastatin may be mainly associated with down-regulation of survivin expression in VSMCs. Up-regulation of Fas in VSMCs may play a role in later stages following atorvastatin treatment.

(2014) Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression, Pharmaceutical Biology, 52:9, 1196-1203, DOI: 10.3109/13880209.2014 . The plasma levels of survivin and sFas were gradually increased with the neointimal hyperplasia and increasingly decreased after atorvastatin treatment. The plasma levels of survivin and sFas in rats were elevated at 3 d (464.80 ± 105.27 pg/ml and 3256.00 ± 478.20 pg/ml, respectively), reached the peak of survivin at 14 d (1089.20 ± 232.32 pg/ml) and sFas at 7 d (4362.00 ± 639.92 pg/ml) and decreased at 28 d (562.00 ± 90.11 pg/ml and 2148.00 ± 257.14 pg/ml, respectively) in the model group. Compared with the model group, the atorvastatin treatment group has significantly less neointimal hyperplasia and more apoptosis of VSMCs. Conclusions: Atorvastatin can inhibit neointimal hyperplasia and promote SMCs apoptosis in neointimal layers, which may be mainly associated with down-regulation of survivin and Fas expression after CAI of rat.

Survivin is essential to angiogenesis and revascularization, but its role in coronary collateral formation remains unclear. The role of survivin in peripheral blood mononuclear cells (PBMCs) of coronary chronic total occlusion (CTO) patients was investigated. Coronary CTO patients (n=46; mean age 60.1±8.5, male 54.3%) (CTO group) and normal control patients (n=18; mean age 58.0±10.0, male 55.6%) underwent angiographic collateral vessel grading by Rentrop classification (C0 – C3) and provided peripheral blood between June 2006 and February 2007. Rat hind limb ischemia models were constructed using four equal groups of Sprague-Dawley rats (n=36): normal control, sham operation, operation and granulocyte macrophage colony-stimulating factor (GM-CSF). PBMC numbers and characteristics, collateral vessels, survivin, CD4, CD8, CD44, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) expression were determined using RT-PCR, flow cytometry, immunocytochemistry and western blot analysis. PBMC survivin mRNA and protein expression levels were higher in patients with good collateral circulation (C2 + C3) than in patients with no collateral flow (C0) (all P<0.05). Survivin single-positive and survivin and CD8, VEGF and ICAM-1 double-positive percentages were elevated in patients with good collateral circulation compared to those with normal and no collateral flow (all P<0.05), consistent with the rat model results, wherein higher survivin levels produced significantly larger and more visible collateral vessels. In conclusion, elevated survivin expression in PBMCs, particularly survivin and CD8, VEGF, and ICAM-1 double-positive PBMCs, may be crucial for good collateral formation in patients with coronary CTO, as confirmed by assessment of a rat model.

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