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Background: Despite significant improvements in stent platform, currently available bare-metal stents (BMS) are still associated with restenosis. Thin-strut design cobalt-chromium alloys hold the promise of improving results of BMS, especially when implanted with direct technique. We performed an observational study to appraise outcomes of the novel Skylor™ stent, stratifying outcomes according to stenting technique., Methods and Results: We included all consecutive patients undergoing coronary stenting with Skylor™ at 2 centers between 2006 and 2009. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e. death, myocardial infarction (MI), coronary artery bypass grafting (CABG) or target vessel revascularization (TVR)). As pre-specified analysis, we compared patients undergoing direct stenting versus those stent implantation following predilation. A total of 1020 patients were included (1292 Skylor™ stents), with procedural success obtained in 99%. Comparing patients undergoing direct stenting (66%) versus pre-dilation (34%) at 16±7 months of follow-up, MACE had occurred in, respectively, 8% versus 14% (p=0.001), with death in 1% versus 2= (p=0.380), MI in 1% versus 2% (p=0.032), CABG in 0.2% versus 2% (p=0.012), and TVR in 6% versus 9% [p=0.071]. Even at multivariable analysis with propensity adjustment, direct stenting was associated with significantly fewer MACE [hazard ratio 0.60 [0.38-0.93], p=0.024]., Conclusions: This observational study suggests the presence of a beneficial synergy between direct coronary stenting technique and use of the novel thin-strut cobalt-chromium Skylor™ stent in real-world patients undergoing PCI.

Objective: Stimuli activating vascular smooth muscle cell death can constrain the neointimal response to arterial damage and prevent vascular thickening. Conversely, endothelial cell death increases endothelial dysfunction and thrombosis risk. We investigated the combined effect of atorvastatin and TNF-α on vascular cell death., Methods and Results: Cell death was investigated in cultures of human aortic smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). Atorvastatin downregulated NF-κB and enhanced JNK activity and cell death in VSMC cultured with TNF- α. In the absence of TNF-α, percentages (mean and StDev) of annexin V positive cells were 17.4 ± 6.6%, 19.3 ± 5.9%, 22.9 ± 9.4% and 35.0 ± 20.0 % with 0, 1, 3 and 10 µM atorvastatin, respectively. The cytotoxic effect of statin was significant at the highest dose of 10 μM (p=0.001). In the presence of TNF-α, percentages of annexin V positive cells were 27.1 ± 10.6%, 34.2 ± 8.5%, 37.4 ± 14.6, and 54.1 ± 20.0% with 0, 1, 3 and 10 µM atorvastatin, respectively. The cytotoxic effect of statin was significant at each dose used (p≤0.02), in the presence of TNF-α. The cell death sensitising effect of atorvastatin was apparently mediated by down modulation of PKCβ activity, because it was reproduced by the specific PKCβ inhibitor LY317615 and prevented by the PKC activator phorbol-12-myristate-13-acetate (PMA). This effect was cell context dependent because it was not observed in HUVECs. PKCβ was found to be constitutively active in VSMCs but not in HUVECs, thereby explaining the differential effect among the two cell types. Measurement of phosphoPKCβ protein levels in arterial specimens confirmed increased activation of this kinase in the smooth muscle layer, in comparison with endothelium. We show that PKCβ provides survival signals to vascular smooth muscle cells and not the endothelium., Conclusion: Our study suggests that atorvastatin enhances TNF-α-induced cell death in vascular smooth muscle- but not endothelial - cells; by a cell-context-dependent mechanism, involving PKCβ inhibition.

CXCR4 is a chemokine receptor implicated in the metastatic process. The CXCR4 ligand, CXCL12, was shown to bind also the CXCR7 receptor, a recently deorphanized chemokine receptor whose signalling pathway and function are still controversial. This study was conducted to determine patients clinic-pathological factors and outcome according to the expressions of CXCR4 and CXCR7 in renal cell carcinoma (RCC). CXCR4 and CXCR7 expression was evaluated in 223 RCC patients through immunohistochemistry; moreover CXCR4 and CXCR7 was detected in 49 others consecutive RCC patients trough RT- PCR. CXCR4 expression was low in 42/223 RCC (18.8%), intermediate in 71/223 (31.9%) and high in 110/223 (49.3%). CXCR7 expression was low in 44/223 RCC patients (19.8%), intermediate in 65/223 (29.1%) and high in 114/223 (51.1%). High CXCR4 and high CXCR7 expression predicted shorter disease free survival. In multivariate analysis, high CXCR4 expression (p= 0.0061), high CXCR7 (p= 0.0194) expression and the concomitant high expression of CXCR4 and CXCR7 (p= 0.0235) are independent prognosis factors. Through RT-PCR, CXCR4 was overexpressed in 36/49 and CXCR7 in 33/49 samples correlating with symptoms at diagnosis and lymph nodes status. So we can hypothesize that CXCR4 and CXCR7, singularly evaluated and in combination, are valuable prognostic factors in RCC patients.