Pleiotropic effects of rosuvastatin on microvascular function in type 2 diabetes Henri K Parson, Meredith A Bundy, Charlotte B Dublin, Amanda L Boyd, James F Paulson, Aaron I VinikLeonard R. Strelitz Diabetes Center, Department of Internal Medicine Eastern Virginia Medical School, Norfolk, Virginia, USA Rosuvastatin is known to reduce low-density lipoprotein (LDL)-cholesterol and improve endothelial function. In addition to lipid-lowering, statins may exert pleiotropic (nonlipid lowering) effects on microvascular function. We compared the neurophysiological and vascular responses of dietary control and treatment with 10 mg of rosuvastatin in 16 subjects with neuropathy and established type 2 diabetes. Skin blood flow (SkBF) measurements were measured at baseline, after 18 weeks of diet, and after 18 weeks of diet and treatment with rosuvastatin in response to local warming and ischemia reperfusion. The study results show that total cholesterol (196.50 ± 8.02 to 134.88 ± 10.86 mg/dL) and LDL-cholesterol (114 ± 10.4 to 63.4 ± 8.48 mg/dL) decreased significantly after 18 weeks of rosuvastatin, but not after 18 weeks of diet. Neuropathy scores decreased from 8.34 ± 1.26 at baseline to 6.00 ± 0.90 after rosuvastatin treatment. Basal SkBF was significantly different from baseline, 6.81 ± 0.42 to 9.92 ± 0.78 after rosuvastatin treatment (P ≤ 0.001). These results indicate that rosuvastatin therapy positively changed basal SkBF and measures of neurovascular function. Although there was a profound lipid lowering, it is not clear that this mediated the increases in SkBF and decreases in neuropathy scores.Keywords: neurovascular function, rosuvastatin, diabetes

Background: Early diagnosis in pancreatic cancer is key for improving prognosis. Hypoxia plays a critical role in tumor progression. Thus, an evaluation of associations between pancreatic tumor progression and markers of hypoxia is needed. Methods: We assessed the expression of hypoxia-inducible factors (HIF-1α and HIF-2α) by immuno-histochemical staining from 29 subjects with the following: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), neuroendocrine tumor (NET), and pancreatic ductal adenocarcinoma (PDAC) and compared it to the expression in non-tumor samples. Results: Expression of HIF-1α increased significantly from PanIN (3.01 ± 0.17) to IPMN (7.63 ± 0.18), NET (9.10 ± 0.23) and PDAC samples (11.06 ± 0.15, p < 0.0001). Similar findings were observed for HIF-2α (p < 0.0001)}. A strong correlation between HIF-1α and HIF-2α expression was demonstrated (R2 = 0.8408, p < 0.0001). Conclusions: This data suggest that HIF-1α and HIF-2α may play a role in the progression from PanIN through PDAC. Further studies are necessary to confirm these findings and determine the effect of HIFs abrogation on tumor progression that can lead to novel therapies.