Autophagy is a complex ''self-eating'' process and could be utilized for cell survival under stresses. Statins, which could reduce apoptosis in mesenchymal stem cells (MSCs) during both ischemia and hypoxia/serum deprivation (H/SD), have been proved to induce autophagy in some cell lines. We have previously shown that atorvastatin (ATV) could regulate AMP-activated protein kinase (AMPK), a positive modulator of autophagy, in MSCs. Thus, we hypothesized that autophagy activation through AMPK and its downstream molecule mammalian target of rapamycin (mTOR) may be a novel mechanism of ATV to protect MSCs from apoptosis during H/SD. Here, we demonstrated that H/SD induced autophagy in MSCs significantly as identified by increasing acidic vesicular organelle-positive cells, type II of light chain 3 (LC3-II) expression, and autophagosome formation. The levels of H/SD-induced apoptosis were increased by autophagy inhibitor 3-methyladenine (3-MA) while decreased by rapamycin, an autophagic inducer. ATV further enhanced the autophagic activity observed in MSCs exposed to H/SD. Treatment with 3-MA attenuated ATV-induced autophagy and abrogated the protective effects of ATV on MSC apoptosis, while rapamycin failed to cause additional effects on either autophagy or apoptosis compared with ATV alone. The phosphorylation of AMPK was upregulated whereas the phosphorylation of mTOR was downregulated in ATV-treated MSCs, which were both attenuated by AMPK inhibitor compound C. Further, treatment with compound C reduced the ATV-induced autophagy in MSCs under H/SD. These data suggest that autophagy plays a protective role in H/SD-induced apoptosis of MSCs, and ATV could effectively activate autophagy via AMPK/mTOR pathway to enhance MSC survival during H/SD.

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Atorvastatin pretreatment can accelerate both neointimal coverage and re-endothelialization after SES implantation, which may be mediated by the mobilization of EPC and enhancement of the endothelial function of the neointima.

Objectives: To investigate the procedure success rate and clinical outcomes of instent restenotic chronic total occlusion (ISR-CTO) percutaneous coronary intervention (PCI).Background: Few studies have reported the short-and long-term clinical outcomes of ISR-CTO PCI.Method: Patients who underwent ISR-CTO (n = 212) or de-novo CTO (n = 2,447) PCI at Fuwai Hospital from 2010 to 2013 were enrolled. Thirty-day and 5-year clinical outcomes were analyzed. The primary outcome was the incidence of all-cause death, myocardial infarction (MI), and heart failure at follow-up. The secondary outcome was the recanalization result (reasonable, suboptimal, or failed recanalization).Results: ISR-CTO PCI had a higher rate of suboptimal recanalization than de-novo CTO PCI (p < .01). The syntax score before PCI (odds ratio (OR): 1.06; 95% confidence interval (CI): 1.02-1.10; p = .002) and occlusion length ≥ 20 mm (OR: 2.70:95% CI: 1.46-4.98; p = .001) were predictors of suboptimal recanalization in ISR-CTO PCI. Cardiac death (p = .03) and 30-day all-cause mortality (p = .05) were higher among patients who underwent ISR-CTO PCI. The ISR-CTO group had a higher rate of MI (p = .07) at 5 years. Suboptimal recanalization (hazard ratio: 2.56; 95% CI: 1.13-5.83; p = .025) was an independent predictor of long-term major adverse events in ISR-CTO.Conclusions: Suboptimal recanalization, 30-day cardiac death, and long-term MI rates are higher for ISR-CTO PCI than de-novo CTO PCI. Suboptimal recanalization is an independent predictor of long-term major adverse events after ISR-CTO PCI.

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