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Background: Restenosis remains to be a major limitation of percutaneous transluminal angioplasty (PTA) for diabetic patients with peripheral vascular disease (PVD). Despite of stations routine implements to prevent such progress, its exact effect is unclear.Methods and Results: In our study, balloon was successfully implanted in the iliac artery of atherosclerotic rabbit. Patency of the narrowed artery was interrogated using ultrasound. Atorvastatin or vehicle was administered orally to rabbits from day 0 to day 28 after double-injury surgery. On day 7, day 14, and day 28, restenotic arteries were harvested and processed for histopathlogical analysis. Our data show that, after double-injury surgery, the intima was composed mostly by SMCs at all time course in rabbits undergoing surgery process. Significant increases in stenosis rates were noted from day 7 to day 14 (from 21 ± 5.85 % to 60.93 ± 12.46 %). On day 28 after double-injury surgery, severe restenosis was observed and daily administration of atorvastatin cannot prevent restenosis' formation (88.69 ± 3.71 % vs. 90.02 ± 3.11 %, P > 0.05). The PCNA index and SMCs proliferation were correlated with the scores of the vascular pathology.Conclusions: Our results indicate that double-injury model can mimic clinical restenosis, based on this model, atorvastatin showed no therapeutic effect on restenosis process in diabetic rabbits after PTA. [ABSTRACT FROM AUTHOR]

Background: Sulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epithelial cells (PTECs) were unclear. Methods: Three commonly used SUs were included in this study to investigate if different SUs have different effects on the apoptosis of PTECs. HK-2 cells were exposed to SUs for 24 h prior to exposure to 30 mM glucose, the apoptosis rate was evaluated by Annexin/PI flow cytometry. Bcl-2, Bax and the ratio of LC3II to LC3I were also studied by western blot in vitro. Diazoxide was used to evaluate the role of KATP channel in SUs-induced apoptosis of PTECs. A Student’s t-test was used to assess significance for data within two groups. Results: Treatment with glibenclamide aggravated the apoptosis of HK-2 cells in high-glucose, as indicated by a significant decrease in the expression of Bcl-2 and increase in Bax. Additionally, the decreased LC3II/LC3I reflects that the autophagy was inhibited by glibenclamide. Similar but less pronounced change was found in glimepiride group, however, nearly opposite effects were found in gliclazide group. Further, the effects of glibenclamide on apoptosis promotion and the decreased LC3II/LC3I were ameliorated obviously by treatment with 100uM diazoxide. The potential protection effect of gliclazide was also inhibited after opening the KATP channel. Conclusion: Our results suggest that, the effects of glibenclamide and glimepiride on PTECs apoptosis, especially the former, were achieved in part by closing the KATP channel. In contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide showed an inhibitory effect on apoptosis of PTECs, which may have a benefit in the preservation of functional PTECs mass. [ABSTRACT FROM AUTHOR]

Background: The effects of statins in patients with diabetic nephropathy are controversial. With increasing interest in the potential therapeutic role of statins in diabetic nephropathy, it is essential to evaluate its real effects., Methods: PubMed, EMBASE, Web of Science databases, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure were systematically searched for randomized controlled trials (RCTs) of statins in patients with diabetic nephropathy., Results: Fourteen trials with 2866 participants were included in our meta-analysis. Compared with placebo, albuminuria and urinary albumin excretion rates in the statin group were reduced by 0.46 [95 % confidence interval (CI),-0.68 to -0.25, P < 0.0001] and 1.68 (95 % CI, -3.23 to -0.12, P = 0.03), respectively. The reduction of albuminuria was greater in patients of type 2 diabetes mellitus with diabetic nephropathy [standardized mean difference (SMD), -0.56; 95 % CI, -0.80 to -0.32, P < 0.00001] and the decrease was significant during the 1 to 3 years period of statin therapy (SMD, -0.57; 95 % CI, -0.95 to -0.19, P = 0.003). Subgroup analysis demonstrated the effects of statins were much stronger in subjects with pathologic albuminuria: change of -0.71 (95 % CI, -1.09 to -0.33, P = 0.0003) for those with urinary protein excretion 30 to 300 mg/day, -0.37 (95 % CI, -0.67 to -0.06, P = 0.02) for those with excretion more than 300 mg/day and -0.29 (95 % CI, -0.78 to 0.21, P = 0.26) for those with excretion less than 30 mg/day. In contrast, statins did not significantly reduce estimated glomerular filtration rate, serum creatinine and blood urea nitrogen levels., Conclusions: Statins decrease the albuminuria and urinary albumin excretion rates significantly. The efficacy of statins on renal function is time dependent and better in type 2 diabetic patients with nephropathy.

Background: Restenosis remains to be a major limitation of percutaneous transluminal angioplasty (PTA) for diabetic patients with peripheral vascular disease (PVD). Despite of stations routine implements to prevent such progress, its exact effect is unclear., Methods and Results: In our study, balloon was successfully implanted in the iliac artery of atherosclerotic rabbit. Patency of the narrowed artery was interrogated using ultrasound. Atorvastatin or vehicle was administered orally to rabbits from day 0 to day 28 after double-injury surgery. On day 7, day 14, and day 28, restenotic arteries were harvested and processed for histopathlogical analysis. Our data show that, after double-injury surgery, the intima was composed mostly by SMCs at all time course in rabbits undergoing surgery process. Significant increases in stenosis rates were noted from day 7 to day 14 (from 21 ± 5.85 % to 60.93 ± 12.46 %). On day 28 after double-injury surgery, severe restenosis was observed and daily administration of atorvastatin cannot prevent restenosis' formation (88.69 ± 3.71 % vs. 90.02 ± 3.11 %, P > 0.05). The PCNA index and SMCs proliferation were correlated with the scores of the vascular pathology., Conclusions: Our results indicate that double-injury model can mimic clinical restenosis, based on this model, atorvastatin showed no therapeutic effect on restenosis process in diabetic rabbits after PTA.

Introduction: Unstable atherosclerotic plaques are prone to rupture, which leads to atherothrombosis. Endothelial progenitor cells (EPCs) are bone marrow-derived precursor cells that may repair vascular injury in atherosclerosis. Chemokine (C-C motif) receptor 5 (CCR5) promotes mobilization of EPCs. In this study, we investigated the therapeutic potential of CCR5-overexpressing EPCs on plaque stabilization in an apolipoprotein E (ApoE)-/- mouse model., Methods: The expression of CCR5 and its cognate ligand chemokine (C-C motif) ligand 5 (CCL5) was examined in atherosclerotic aortas of humans and mice by immunohistochemistry. Splenectomized ApoE-/- C57BL/6 J mice fed a high-fat diet for 24 weeks were intravenously injected with EPCs transfected with CCR5 overexpression lentivirus. The recruitment of EPCs over the atherosclerotic plaques was evaluated by immunofluorescence. The content of lipid, smooth muscle cells, monocytes/macrophages, and endothelial cells in atherosclerotic plaques was assayed by specific immunostaining. The serum levels of atherosclerosis-related inflammatory factors in ApoE-/- mice were measured by mouse atherosclerosis antibody array I., Results: CCR5 and CCL5 are highly expressed in atherosclerotic plaques in both humans and mice. The ApoE-/- mice with CCR5-overexpressing EPC treatment demonstrated a more stable plaque formation with enhanced recruitment of EPC, reduced lipid, and macrophage content in the atherosclerotic plaques. CCR5-overexpressing EPC treatment also increased the content of endothelial cells and nitric oxide production in the plaques. In addition, the serum levels of interleukin-3 (IL-3), IL-5, IL-6, IL-13, CD40, and tumor necrosis factor-alpha and the plaque contents of IL-6 and matrix metalloproteinase-9 were reduced in mice with CCR5-overexpressing EPC treatment., Conclusions: These findings suggest that CCR5 is a novel therapeutic target in EPC treatment for stabilization of atherosclerotic plaques.