The present research and progress of angiopoietin in diabetic retinopathy / 中华眼底病杂志

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and it is the main cause of vision loss in diabetic patients. Angiopoietin (Ang), a superfamily of secreted proteins, is a vascular growth factor that regulates the stability of vascular environment, participates in angiogenesis and repair, and lipid metabolism. It plays an important role in the development of DR and has become a new target for the treatment of diabetic retinopathy. With the in-depth study of Ang and the research and development of various drugs for Ang, it is expected to bring new ideas and strategies for the treatment of DR in the future.

Role of angiopoietin-like proteins in the development of nonalcoholic fatty liver disease / 临床肝胆病杂志

Angiopoietin-like proteins (ANGPTLs) are a family of secretory glycoproteins recently found to be constitutionally homologous with angiogenin and play a role in the regulation of angiogenesis. In recent years, more and more studies have shown that ANGPTLs play an important role in glucose and lipid metabolism, inflammation, and tumor. As we all know, nonalcoholic fatty liver disease and its disease spectrum are closely associated with metabolism, inflammation, and tumor. This article reviews the role of ANGPTLs in various diseases associated with nonalcoholic fatty liver disease, in order to provide new ideas for the prevention and treatment of nonalcoholic fatty liver disease in clinical practice.

The correlation of serum cartilage glycoprotein 39 and angiopoietin-like protein 3 levels with left ventricular dysfunction in elderly patients of coronary heart disease with heart failure / 中华老年医学杂志

Objective:To analyze the relationship of serum cartilage glycoprotein 39(YKL-40)and angiopoietin-like protein 3(ANGPTL3)with left ventricular dysfunction in elderly coronary heart disease(CHD)patients with heart failure(HF).Methods:The 84 elderly patients divided into group of CHD with HF, and 80 patients divided into group of CHD without HF treated in Shekou People's Hospital of Nanshan District, Shenzhen City from January 2018 to December 2019 were enrolled in this study.Evaluation of the left ventricular function meets the cardiac function classification standard of(NYHA). Serum YKL-40 and ANGPTL3 levels in all patients were detected.The relationships of serum YKL-40 and ANGPTL3 levels with the left ventricular dysfunction were analyzed in the two groups.Results:Serum levels of YKL-40 and ANGPTL3 were higher in the group of CHD with HF than in the group of CHD without HF[(81.24±6.32)μg/L vs.(69.33±5.89)μg/L, and(42.40±5.03)μg/L vs.(30.25±4.23)μg/L, t=12.469 and 16.700, both P<0.001]. Of 84 patients of CHD with HF assessed by NYHA heart function, 35 cases were in the mild group and 49 cases were in the severe group.Logistic regression analysis showed that the elevated serum level of serum YKL-40 and ANGPTL3 was positively correlated with the severity of left ventricular dysfunction in patients of CHD with heart failure( OR=1.548 and 1.854, P=0.002 and 0.001). The receiver operator characteristic(ROC)curve showed that the area under the ROC curve(AUC)of YKL-40, ANGPTL3 alone and the combined index in predicting left ventricular dysfunction in CHD with heart failure were >0.80, and the best predictive value could be obtained when the cut-off values of YKL-40 and ANGPTL3 were 79.535 μg/L and 40.805 μg/L, respectively. Conclusions:The elevated serum level of YKL-40 and ANGPTL3 may indicate the more severe left ventricular dysfunction in patients of CHD with heart failure.Early monitoring of serumYKL-40 and ANGPTL3 levels has an important clinical significance in guiding early prediction and intervention of left ventricular dysfunction in patients of CHD with heart failure.

Serum expression of angiopoietin-like protein 2 in pancreatic cancer patients with or without diabetes and its association with prognosis / 临床肝胆病杂志

ObjectiveTo investigate the expression level of angiopoietin-like protein 2 (ANGPTL2) in pancreatic cancer patients with or without diabetes and the clinical value of ANGPTL2 as a prognostic marker in patients with pancreatic cancer. MethodsSerum samples were collected from 125 pancreatic cancer patients who were treated in The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Cancer Hospital, and Wuming Hospital of Guangxi Medical University from January 2015 to January 2018, among whom 64 had pancreatic cancer alone and 61 had pancreatic cancer and diabetes, and 66 individuals who underwent physical examination were enrolled as control group. ELISA was used to measure the serum level of ANGPTL2, and the association of the expression level of ANGPTL2 with clinical indices, survival, and prognosis was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups, and the Bonferroni test was used for comparison between two groups. The independent-samples Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between three groups and the one-way ANOVA analysis was used for comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Spearman correlation analysis was also performed to investigate correlation. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rate. The Cox risk model was used to perform univariate and multivariate analyses to determine independent risk factors for the prognosis of pancreatic cancer. ResultsThe pancreatic cancer+diabetes group had a significantly higher serum concentration of ANGPTL2 than the pancreatic cancer group and the control group ［7.79 (7.12-8.17) ng/ml vs 5.74 (508-6.40) ng/ml and 3.72 (3.25-4.16) ng/ml, χ2=126.367, P＜0.001］. Serum ANGPTL2 concentration was positively correlated with carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) (r=0.560 and 0.731, both P＜0.001). The univariate analysis showed that tumor size, distant organ metastasis, degree of tumor differentiation， CEA, ANGPTL2, and HbA1c were closely associated with the long-term survival of pancreatic cancer patients, and the multivariate analysis showed that tumor size (HR=2.657,P=0.005), distant organ metastasis (HR=5.000,P=0.014), degree of tumor differentiation (HR=2.466,P=0.004), CEA(HR=1.110,P＜0.001) and ANGPTL2(HR=1.901,P=0.001) were independent risk factors for the prognosis of pancreatic cancer patients. For all pancreatic cancer patients, the high ANGPTL2 expression group had a significantly lower 2-year survival rate than the low ANGPTL2 expression group (8.51% vs 25.81%, χ2=5.651, P=0.017). For the pancreatic cancer patients with diabetes, the high ANGPTL2 expression group had a significantly lower 2-year survival rate than the low ANGPTL2 expression group (2.20% vs 32.70%, χ2=24.895, P＜0.001).ConclusionANGPTL2 can be used as an effective clinical index to evaluate the prognosis of pancreatic cancer patients, especially those with diabetes.

Pathophysiology of Diabetic Retinopathy: The Old and the New

Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.

Inhibitory effect of angiogenin on the expression of type Ⅰ collagen and fibronectin in dermal papilla cells from androgenetic alopecia areas / 中华皮肤科杂志

Objective To evaluate effects of angiogenin on the expression of type Ⅰ collagen and fibronectin in dermal papilla cells from androgenetic alopecia areas,and to explore its possible mechanisms.Methods Dermal papilla cells were isolated from androgenetic alopecia areas and cultured.Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of androgen receptor in dermal papilla cells of different passages,and cell counting kit-8 (CCK-8) assay to evaluate the effect of angiogenin at different concentrations of 0,10,20,40,80,160 μg/L on the proliferative activity of the dermal papilla cells cultured in a medium with or without 0.1 nmol/L dihydrotestosterone.The confluent first-passage dermal papilla cells were divided into 3 groups:control group receiving no treatment,dihydrotestosterone group treated with 0.1 nmol/L dihydrotestosterone,and dihydrotestosterone + angiogenin group treated with 0.1 nmol/L dihydrotestosterone and 80 μg/L angiogenin.After 48-hour treatment,realtime fluorescence-based quantitative PCR was conducted to measure the mRNA expression of type Ⅰ collagen gene,fibronectin and transforming growth factor-β1 (TGF-β1),and Western blot analysis to determine the protein expression of type Ⅰ collagen,fibronectin,TGF-β1,phosphorylated Smad2 (p-Smad2) and p-Smad3.Statistical analysis was done by one-way analysis of variance (ANOVA),least significant difference (LSD)-t test and t test for two independent samples.Results The mRNA expression of androgen receptor significantly decreased during the subcultivation of in vitro cultured dermal papilla cells from androgenetic alopecia areas (P ＜ 0.05).Cell proliferation assay showed that 20-160 μg/L angiogenin could evidently antagonize the inhibitory effect of 0.1 nmol/L dihydrotestosterone on the proliferation of dermal papilla cells (all P ＜ 0.05).Compared with the control group,the dihydrotestosterone group showed significantly higher mRNA expression of type Ⅰ collagen gene,fibronectin and TGF-β1.However,the mRNA expression of type Ⅰ collagen gene,fibronectin and TGF-β1 was significantly lower in the dihydrotestosterone + angiogenin group than in the dihydrotestosterone group (type Ⅰ collagen gene:1.563 ± 0.143 vs.4.329 ± 0.165;fibronectin:1.290 ± 0.063 vs.2.156 ± 0.115;TGF-β1:1.136 ± 0.098 vs.1.707 ± 0.100;all P ＜ 0.05).Moreover,angiogenin could obviously suppress the expression of type Ⅰ collagen,fibronectin,TGF-β1,p-Smad2 and p-Smad3 protein by dihydrotestosterone-induced dermal papilla cells (all P ＜ 0.05).Conclusion Angiogenin can inhibit the expression of type Ⅰ collagen and fibronectin in dermal papilla cells from androgenetic alopecia areas in vitro,which may be associated with the downregulated expression of TGF-β1 and inhibition of TGF-β1/Smad signaling pathway.

Mechanism underlying docosahexaenoic acid-induced regulation of angiopoietin expression in human brain vascular pericytes subjected to oxygen-glucose deprivation and restoration: the relationship with SSeCKS / 中华麻醉学杂志

Objective To evaluate the relationship between the mechanism underlying docosahexaenoic acid (DHA)-induced regulation of angiopoietin expression and Src-suppressed C kinase substrate (SSeCKS) in human brain vascular pericytes (HBVPs) subjected to oxygen-glucose deprivation and restoration (OGD/R).Methods HBVPs were seeded in 96-well or in 6-well plates at a density of 2× 105 cells/ml and divided into 5 groups (n =18 each) using a random number table:control group (group C),OGD/R group,DHA group (group D),SSeCKS gene silencing group (group S) and SSeCKS gene silencing plus DHA group (group SD).The model of OGD/R injury was established as follows:the cells were subjected to O2-glucose deprivation for 24 h in glucose-and serum-free culture medium aerated with 94％ N2-5％ CO2-1％ O2 followed by restoration of O2-glucose supply for 6 h in high-glucose DMEM culture medium in normal atmosphere.DHA was added at 1 h before hypoxia with the final concentration of 40 μmol/L in group D.Small interfering RNA induced SSeCKS gene silencing in S and SD groups.Subsequently,DHA with the final concentration of 40 μmol/L was added at 1 h before hypoxia in group SD.At 6 h of reoxygenation,the cell survival rate was determined by CCK-8 assay,the amount of LDH released was detected using ELISA,and the expression of SSeCKS,angiopoietin-1 (Ang-1) and Ang-2 was detected by Western blot.Results Compared with group C,the cell survival rate was significantly decreased,the amount of LDH released was increased,the expression of SSeCKS and Ang-1 was down-regulated,the expression of Ang-2 was up-regulated,and Ang-1/Ang-2 ratio was decreased in group OGD/R,and the expression of SSeCKS was down-regulated in group S (P＜0.05).Compared with group OGD/R,the cell survival rate was significantly increased,the amount of LDH released was decreased,the expression of SSeCKS and Ang-1 was up-regulated,the expression of Ang-2 was down-regulated,and Ang-1/Ang-2 ratio was increased in group D (P＜O.05),and no significant change was found in the parameters mentioned above in group SD (P＞0.05).Compared with group D,the cell survival rate was significantly decreased,the amount of LDH released was increased,the expression of SSeCKS and Ang-1 was down-regulated,the expression of Ang-2 was up-regulated,and Ang-1/Ang-2 ratio was decreased in group SD (P＜0.05).Conclusion The mechanism by which DHA increases the ratio of Ang-1/Ang-2 may be totally related to up-regulation of SSeCKS expression in HBVPs subjected to OGD/R.

Expressions and Clinical Significances of Angiopoietin-1, Angiopoietin-2, and Tie-2 Receptor in Patients With Colorectal Cancer

PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. METHODS: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. RESULTS: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). CONCLUSION: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.

The study of the changes in serum concentrations of angiogenic factors in patients with unstable angina pectoris / 中国医师杂志

Objective To explore the changes in serum concentrations of angiogenic factors in patients with unstable angina pectoris.Methods A total of 60 patients with unstable angina pectoris was eligible for study and divided into diabetes group ( A group, n =20) and non-diabetes group (B group, n =40).Another 30 general-matched healthy subjects from medical examination center were enrolled as control group .Serum samples were collected , and serum concentrations of vascular endothelial growth factor (VEGF), angiopoietin-1, angiopoietin-2, angiogenin, angiostatin, basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB ( PDGF-BB) were measured by cytokine array technology and compared between the groups .Results Compared with the control group, the serum concentrations of VEGF [(325.2 ±210.1)pg/ml] and angiopoietin-2 [(3031.3 ±1865.5)pg/ml] were sig-nificantly increased in patients with unstable angina pectoris (both P <0.05).Whereas,no significant differences in serum concentra-tions of angiogenin,angiopoietin-1,angiostatin,bFGF,and PDGF-BB were detected between control group and patient groups .There were no significant differences in serum concentrations of above all 7 biomarkers between diabetes group and non-diabetes group .Con-clusions Serum concentrations of VEGF and angiopoietin-2 were increased in patients with unstable angina pectoris ,and diabetes didn't affect the increases in serum concentrations of VEGF and angiopoietin-2 caused by unstable angina pectoris .

Expression of angiogenic factors in myocardial tissue of diabetic rats / 中国病理生理杂志

AIM:To observe the expression of angiogenesis factors in the myocardial tissue of streptozotocin-induced diabetic rats .METHODS:The diabetic rat model was induced by intraperitoneal injection of streptozotocin .After 12 weeks, the cardiac function was measured by MPA cardiac function analysis system .The myocardial collagen volume fraction ( CVF) was assessed by Masson staining .The capillary vessels was quantified as the ratio of capillary to myocyte (C/M) using CD31 immunostaining.The expression levels of vascular endothelial growth factor (VEGF), angiopoietin ( Ang)-1, endostatin and Ang-2 were observed by Western blotting .RESULTS:Compared with normal control group , the left ventricular end-diastolic pressure (LVEDP) was evidently increased (P0.05).CONCLUSION:Im-balances between the angiogenic factors (VEGF and Ang-1) and anti-angiogenic factors (endostatin) may play an impor-tant role in the pathogenesis of diabetic cardiomyopathy .

The roles of exosomes in the tumor microenvironment / 国际外科学杂志

The tumor microenvironment is a special environment including tumor cells,stromal cells and extracellular matrix.The notion that the tumor microenvironment is a necessary functional unit to support cancer progression,metastasis and recurrence has been accepted by more and more scholars.Studies have shown that exosomes may play a pivotal role in tumor progression that involved in cell-cell communication in the tumor microenvironment.Here,we summarize the recent publications on the characteristics of exosomes,its biological effects and the potential roles as an important part of the tumor microenvironment during tumor progression.

Avaliação clínica de proteínas modeladoras da permeabilidade endotelial como biomarcadores para estratificação de risco na sepse em pacientes com neoplasias hematológicas e neutropenia febril / Clinical evaluation of modulators of endothelial permeability as biomarkers for risk stratification in sepsis patients with hematological malignancies and febrile neutropenia

A neutropenia febril (NF) em pacientes com neoplasias hematológicas é caracterizada pelo alto risco de sepse e choque séptico. Embora a utilização de escores clínicos como o MASCC permita a identificação de pacientes de baixo risco, este escore é menos informativo em pacientes de alto risco, onde se encaixam a maioria dos pacientes com neoplasias hematológicas, além daqueles submetidos a esquemas intensivos de quimioterapia. Ao mesmo tempo, a aplicação de biomarcadores de gravidade como a procalcitonina, validados em pacientes não-neutropênicos, é controversa em pacientes com NF. A quebra da barreira endotelial é um elemento chave no choque séptico, de modo que proteínas envolvidas neste processo são candidatos atrativos como biomarcadores de gravidade na sepse. Neste estudo, avaliamos prospectivamente o valor da dosagem de VEGF-A, sFlt-1, Ang-1 e Ang-2 como biomarcadores da evolução para choque séptico em 120 pacientes com NF. Pacientes internados nas enfermarias de Hematologia e Transplante de Medula Óssea do HC da UNICAMP para tratamento de NF entre março de 2011 e 2012 foram convidados a participar. As amostras foram coletadas na manhã seguinte à entrada no estudo, junto com a coleta de exames de rotina. O estudo foi desenhado com o objetivo de mimetizar as condições de coleta e processamento das amostras, que seriam encontradas na prática clínica real. Foi avaliada a evolução para choque séptico e mortalidade em 28 dias. Os resultados foram comparados com marcadores de prognóstico clássicos como proteína C reativa, e escores MASCC e SOFA. No total, 99 pacientes preencheram os critérios de inclusão, dos quais 19,8% evoluíram com choque séptico. Não foram observadas diferenças clínicas e demográficas entre os pacientes com NF não-complicada e choque séptico, exceto pelo escore SOFA, significativamente mais elevado no segundo grupo.

Febrile neutropenia (FN) in patients with hematologic malignancies is characterized by a high risk of sepsis complications and septic shock. Although the use of clinical scores such as the MASCC allows the identification of low-risk patients, this score is much less informative in high-risk patients, a category in which most patients with hematologic malignancies, and those undergoing intensive chemotherapy regimens, fit in. At the same time, the use of classical biomarkers such as procalcitonin in non-neutropenic patients is controversial in patients with FN. Endothelial barrier breakdown is a key element in septic shock, so that proteins involved in this process are attractive candidates as biomarkers of sepsis severity. In this study, we prospectively evaluated the value of VEGF-A, sFlt-1, Ang-1 and Ang-2 serum levels as biomarkers of progression to septic shock in 120 patients with FN. Patients hospitalized in the Hematology and Bone Marrow Transplantation in-patient units of a university hospital (HC-UNICAMP) for the treatment of FN between March 2011 and March 2012 were invited to participate. Samples were collected in the following morning after study entry, along with the collection of routine labs. The study was designed to mimic the conditions of blood sample collection and processing that would be encountered in "real-world" clinical practice. Clinical outcomes were (1) progression to septic shock and (2) death within 28 days from fever onset. Results were compared with classical prognostic markers such as C-reactive protein, and MASCC and SOFA scores. In total, 99 patients met the inclusion criteria, of which 19.8% progressed to septic shock. No differences clinical and demographic differences were observed between patients with uncomplicated-FN or septic shock, except for a higher SOFA scores in the latter group.

Expression and clinical significance of EphA8 in colon cancer / 国际肿瘤学杂志

Objective To investigate the expression of EphA8 in colon cancer and its clinical significance.Methods Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot were respectively used to assess the expressions of EphA8 mRNA and protein in normal colon mucosa cell line and colon cancer cell lines.Immunohistochemistry for EphA8 and vascular endothelial growth factor (VEGF) were performed in 98 cases of colon cancer and 12 matched normal mucosa tissues.CD31 immunohistochemical staining was used for microvascular density (MVD) counting.The relationships between the expression of EphA8 and the expression of VEGF and MVD,the clinical pathological significance,and the prognosis of patients were analyzed by statistical methods.Results EphA8 mRNA expressions were significantly higher in colon cancer cell lines than those in normal mucosa cell line (t =11.98,13.54,P ＜0.001).EphA8 protein expressions were significantly higher in colon cancer cell lines than those in normal mucosa cell line (t =4.63,P =0.006;t =4.92,P =0.004).The high expression of EphA8 was closely related to tumor size (x2 =22.97,P＜0.001),TNM stage (P＜0.001),differentiated degree (P =0.007)and lymph node metastasis (P＜0.001),distant metastasis (x2 =6.97,P =0.008) and poor survival rote (x2 =17.3,P ＜0.001).But it was not associated with the gender and age (x2 =1.36,P =0.30; x2 =0.83,P=0.44).Besides,EphA8 had positive correlation with the VEGF and MVD (r =0.434,P ＜0.001; r =0.584,P ＜0.001).Conclusion EphA8 may play important roles in the development and metastasis of colon cancer,which has potential clinical values in the therapeutic intervention and prognosis of colon cancer.

Identification of Novel Drug Targets for the Treatment of Diabetic Retinopathy

Vision loss in diabetic retinopathy (DR) is attributable to retinal vascular disorders that result in macular edema and neoangiogenesis. In addition to laser photocoagulation therapy, intraocular injections of antivascular endothelial growth factor drugs have contributed to the treatment of these disease conditions. Nonetheless, the clinical feasibility of intraocular drug administration has raised an increasing demand to develop alternative drugs that can fundamentally ameliorate the retinal vascular dysfunctions in DR. For this purpose, experimental animal models that reproduce human DR would be of clinical benefit. Despite the unavailability of DR models in rats or mice, pharmacological and genetic manipulations without hyperglycemia have successfully recapitulated retinal edema and neoangiogenesis in postnatal mouse retinas, thereby enabling the understanding of the pathophysiology underlying DR. This article highlights the utility of experimental mouse models of retinal vascular abnormalities and discusses cellular and molecular mechanisms responsible for the onset and progression of DR. These approaches will lead to the identification of novel drug targets for the restoration of vascular integrity and regeneration of functional capillaries in DR.

Angiopoietin-2 and tumor angiogenesis / 国际肿瘤学杂志

Tumor angiogenesis is an important way of rapid proliferation and metastasis for malignancies,and a variety of cellular and molecular factors involved in the process.Angiopoietin-2(Ang-2) is one of the important vascular endothelial growth factor,which influences tumor angiogenesis mainly through releasing vascular structures and damaging the vessel stability.Recent researches reveal that Ang-2 modulates tumor angiogenesis interacting with other vascular growth factors.With the new research progress,Ang-2 will not only be an important target for antiangiogenic therapy,but also further improve clinical efficacy of antitumor therapy combined with other signal pathways as common targets.

Hypoxia-inducible factor-l attributing to tumor angiogenesis / 国际肿瘤学杂志

Hypoxia-inducible factor-1 ( HIF-1 ) is one of the most important transcriptional factors which regulate the transcription of vascular endothelial growth factor ( VEGF ), HIF-1 plays a critical role in tumor angiogenesis and metastasis. The transcriptional regulation role for HIF-1 in tumor angiogenesis is closely related to its molecular structure,biological character and molecular mechanism and signaling pathways.

Angiogenic growth factor responses to long-term treadmill exercise in mice.

We sought to determine whether VEGF and other angiogenic growth factors and their receptors might be subject to negative feedback regulation during two weeks of treadmill-exercise conditioning in inbred strains of mice. C57BL/6 mice exhibited greater VEGF mRNA and protein responses in gastrocnemius muscle to a single bout of treadmill exercise compared to BALB/c mice. The patterns of VEGF, VEGFR1, VEGFR2, Ang2 and Tie2 mRNA expression in gastrocnemius muscles of C57BL/6 mice during long-term exercise support the hypothesis that they may be subject to negative feedback regulation. The combination of expression patterns for growth factors and their receptors suggests that multiple layers of control mechanisms may exist to prevent angiogenesis following a single bout of exercise and to promote angiogenesis following long-term exercise.

Expression of angiogenin in human hair follicle and its effect on hair growth / 中华皮肤科杂志

Objective To investigate the expression of angiogenin in human hair follicle and evaluate its effect on hair growth. Methods Intact anagen hair follicles were isolated from human occipital scalp ob- tained from brain surgery. Some isolated human hair follicles were directly subjected to RT-PCR and im- munohistochcmical method for the detection of the mRNA expression and protein distribution of angiogenin in, respectively; some were cultured and incubated with angiogenin (0-200 ng/mL), and the measurement of hair follicle length was performed before and after 6-day culture. Human dermal papilla cells were isolated from the remaining hair follicles, cultured, and treated with angiogenin ranging from 0 to 200 ng/mL for 48 hours, then, MTT assay was used to detect the cell proliferation, and flow cytometry to analyze the cell cy- cle. Results RT-PCR showed the mRNA expression of angiogenin in human hair follicles, and angiogenin protein was observed with immunohistochemistry at the hair papilla and dermal sheath. The angiogenin (25-200 ng/mL) stimulated the growth of human hair follicles in a dose-dependent manner in vitro (P < 0.05 ). Also, as flow eytometry revealed, the treatment with 12.5-200 ng/mL of angiogenin significantly pro- moted the proliferation of human dermal papilla cells (P<0.05), and increased the percentage of cells in S phase as well as cell proliferation index (both P<0.05). Conclusion Angiogenin may be a novel stimulus for hair growth.

Expression of angiogenesis regulatory factors and their receptors in mouse kidneys with aging / 中华肾脏病杂志

Objective To investigate the expression of vascular endothelial growth factor (VEGF), angiopoietin and their receptors (VEGFR and Tie2) in aging mice kidney and the possible roles in aging mice. Methods Mice were divided as follows: 4-month old group (n=6), 9-month old group (n=6), 12-month old group (n=6) and 20-month old group (n=6). Paraffin sections of the mice kidneys were stained by PAS. The density of glomerular microvascular was determined by renal perfusion with fluorescent dyes. The level of VEGF, VEGFR2 (Flk-1), Ang-1, Ang-2, Tie2 mRNA expression and protein abundance in kidney was determined by real-time PCR, immunochemistry, immunofluorescence and Western blot. Results Compared with other three groups, in the 20-manth old group, the glomerulosclerosis index (GSI) increased remarkbly (2.48±0.79 vs 0.53±0.19, 0.69±0.18, 1.50±0.70, P<0.05); the fluorescence intensity in glomeruli decreased (P<0.05). lmmunohistochemistry demonstrated that the TGF-131 level in the aging kidneys showed an increase trend in the glomerular tubulointerstitium, and especially in the glomeruli. Real-time PCR results revealed that compared with 4-month old group mice, the mRNA expression of VEGF, Flk-1, Ang-1, Ang-2, Tie2 of the other three groups decreased, the gene levels of VEGF, Flk-1, and Ang-2 fell about 90%, 50% and 80% (all P>0.05), and the gene levels of Ang-1 and Tie2 fell about 75% and 40% in 20-month-old group (all P<0.05). Western blot domonstrated that the protein abundace of VEGF, Flk-1, Ang-1, Ang-2, Tie2 also declined with aging, the protein level of VEGF, Flk-1, Ang-1, Ang-2 and Tie2 dropped by about 35%, 50%, 15%, 13% and 21% respectively in 20-month-old group as compared to 4-month-old group (all P<0.05). Expression of above 5 factors and glomerular fluorescence intensity were negatively correlated with Scr (P<0.05). Conclusions The mRNA expression and protein abundance of VEGF, Flk-1, Ang-1, Ang-2, Tie2 in mice kidneys decreases with aging. Angiogenesis regulatory factors may play important roles in aging progression of the mice kidney.

Transplantation of autologous bone marrow mesenchymal stem cells transfected by angiogenin gene in a porcine chromic ischemic heart model / 中华胸心血管外科杂志

Objective To investigate the effect of the transplantation of autologous marrow mesenchymal stem cells transfected by angiogenin gene in a porcine chronic ischemic beart model.Methods Methods Mesenchymal stem cells were trnsfected byAd/Ang.The pigs underwent placement of amerold occluder around LCx and 4 weeks later sujected to transplantation of the trandected mesenchymal stem cells.The animals were evaluated by coronary angiography,echocardiography,mannetic resonance imaging end pathologic observation.Results All animal showed 95%occlusion fo LCx.4 weeks after treatment ,the perfusion of LCx,left ventricular ejection fracton were greatly evhanced.A large number of labeled mesenchymal stem cells were successfully uncorporated into blood vessels in the ischemic myocardial regions with increased vessels countin and survival of implanted cell.Conclusion Transplantaton of autologous mesenchymal stem cells trendected by angiogenin gene offere obvious advsntases of great improvement of blood supply and the heart funcition.