Effects of natural mineral-rich water consumption on the expression of sirtuin 1 and angiogenic factors in the erectile tissue of rats with fructose-induced metabolic syndrome

Consuming a high-fructose diet induces metabolic syndrome （MS）-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular disease. Because mineral deficiency intensifies the deleterious effects of fructose consumption and mineral ingestion is protective against MS, we aimed to characterize the effects of 8weeks of natural mineral-rich water consumption on the structural organization and expression of vascular growth factors and receptors on the corpus cavernosum （CC） in 10% fructose-fed Sprague-Dawley rats （FRUCT）. Differences were not observed in the organization of the CC either on the expression of vascular endothelial growth factor （VEGF） or the components of the angiopoietins/Tie2 system. However, opposing expression patterns were observed for VEGF receptors （an increase and a decrease for VEGFR1 and VEGFR2, respectively） in FRUCT animals, with these patterns being strengthened by mineral-rich water ingestion. Mineral-rich water ingestion （FRUCTMIN） increased the proportion of smooth muscle cells compared with FRUCT rats and induced an upregulatory tendency of sirtuin I expression compared with the control and FRUCT groups. Western blot results were consistent with the dual immunofluorescence evaluation. Plasma oxidized low-density lipoprotein and plasma testosterone levels were similar among the experimental groups, although a tendency for an increase in the former was observed in the FRUCTMIN group. The mineral-rich water-treated rats presented changes similar to those observed in rats treated with MS-protective polyphenol-rich beverages or subjected to energy restriction, which led us to hypothesize that the effects of mineral-rich water consumption may be more vast than those directly observed in this study.

Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats

The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.

CCR7/p-ERK1/2/VEGF signaling promotes retinal neovascularization in a mouse model of oxygen-induced retinopathy

AIM： To investigate the role of CCR7/p-ERKI/2/VEGF signaling in the mouse model of oxygen-induced retinopathy （OIR）. METHODS： Neonatal C57BL/6J mice were evenly randomized into four groups： normoxia, OIR, OIR control （treated with scramble siRNA）, and OIR treated （treated with CCR7 siRNA）. Normoxia group was not specially handled. Postnatal day 7 （P7） mice in the OIR group were exposed to 75%±5% oxygen for 5d （P7-P12） and then maintained under normoxic conditions for 5d （P12-P17）. Mice in the OIR control and OIR treated groups were given injections of scramble or CCR7 siRNA plasmid on P12 before returning to normoxic conditions for 5d （P12-P17）. Retina samples were collected from all mice on P17, stained with adenosine diphosphatase （ADPase）, and retinal neovascularization （RNV） was assessed. Retinas were also stained with hematoxylin and eosin （H＆E） for RNV quantitation. The distribution and expression of CCR7, p-ERKI/2 and vas- cular endothelial growth factor （VEGF） were assessed via immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR）. RESULTS： High oxygen promoted retinal neovascularization （P〈0.05） and increased the number of endothelial nuclei in new vessels extending from the retina to the vitreous body; CCR7 promoted this process （P〈0.05）. CCR7 and VEGF mRNA were expressed at higher levels in the OIR and OIR control groups than in the normoxia and OIR treated groups. CCR7, p-ERK1/2, and VEGF protein were expressed in the retinas of mice in the OIR and OIR control groups. Intravitreal injection of CCR7 siRNA significantly reduced CCR7, p-ERKI/2, and VEGF expression in the OIR mouse model （all P〈0.05）. CCR7 significantly enhancedthe neovascularization and non-perfusion areas in the OIR group （P〈0,05）, CCR7 siRNA significantly reduced levels of p-ERK1/2 and VEGF as compared to OIR controls （P〈0.05）. CONCLUSION： These results suggest that CCR7/p-ERK I/2NEGF signaling plays an important role in OIR, CCR7 may be a potential target for the prevention and treatment of retinopathy of prematurity.

Correlation of MR Perfusion-weighted Imaging of Prostatic Cancer with Tumor Angiogenesis

Objective： MR perfusion-weighted imaging（PWI） has been widely applied in the research of cerebral tumor, benign and malignant musculoskeletal neoplasms and so on. The aim of this study is to explore the application of MR perfusion-weighted imaging in prostatic cancer （Pca）, and evaluate the correlation of PWI features with vascular endothelial growth factor （VEGF） and microvessel density （MVD）. Methods： Twenty-eight consecutive patients who were diagnosed clinically as prostatic cancer and thirty healthy volunteers were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWI, including the steepest slope of signal intensity-time curve （SSmax） and the change in relaxation rate （ΔR2^＊peak） at lesions, were analyzed. Correlation analysis was used to determine the relationship between the results of PWI and that of immunohistochemistry. Results： （1） In the healthy volunteers, the steepest slope of signal intensity-time curve （SSmax） and ΔR2^＊peak of perfusion curve were： 0.430±0.011, 2.01±0.7 respectively; however, in the prostatic cancer, they were 57.8±5.0, 3.0±0.6 respectively; with significant difference （t=-4.11, 3.28, P〈0.01）. （2）The VEGF and MVD expression of twenty-eight Pca patients were significantly higher. Conclusion： On MR perfusion- weighted imaging, SSmax and ΔR2^＊peak can reflect MVD and VEGF expression levels in prostatic cancer, suggesting information on tumor angiogenesis. Thus they are beneficial to the diagnosis and treatment of prostatic cancer.

Effects of ivabradine on the levels of HIF-1α and VEGF in serum of rabbit with acute myocardial infarction

The study aimed to investigate the effects of ivabradine on the levels of hypoxia-inducible factor-lalpha （HIF-1α） and VEGF in serum of rabbit with acute myocardial infarction （AMI）. Methods AMI model was established by ligating the left anterior descending branch of the coronary artery in New Zealand white rabbits. Twenty five rabbits were randomly divided into 4 groups： sham-operated （S）, myocardial-infarction （M） with bisoprolol treatment （M ＋ B） and ivabradine-treated （I ＋ M）. The medical treatment began immediately after infarction and continued for 3 weeks. Serum of each rabbit was obtained at the following time points （24 h before the operation, 24 h, 3 d, 1 week, 2 weeks and 3 weeks after the operation）. ELISA was used to measure the levels of HIF-1α and VEGF of each sample. ECG and heart rates （before and after treatment） were analyzed. Results Baseline heart rate showed no significant differences between the 3 infarcted groups （M, M ＋ B, M ＋ I）. Three weeks later the heart rates were significantly lower in group M ＋ B and group M ＋ I than in group M. However, there was no statistic difference between the two drug-treated groups （P = 0.848）. The levels of HIF-1α and VEGF in groups M, M ＋ B and M ＋ I） increased significantly compared with group S （P 〈 0.01）. The productions of HIF-1α and VEGF were lower in group M ＋ B and group M ＋ I compared with group M （P 〈 0.01）. There was no statistical difference between the group M ＋ B and group M ＋ I （P 〉 0.05）, and the correlative analysis revealed that the production of HIF-1α was positively correlated with that of VEGF （r = 0.732, P 〈 0.01）. Conclusion Ivabradine can reduce heart rate and meanwhile decrease the serum levels of HIF-1α and VEGF after AMI.