angiogenin and Chronic-Disease

The efficacy and safety of gene-engineering recombinant constructions with endothelial growth factor gene and angiogenin for the treatment of the chronic lower limb ischemia were studied. 134 patients were included in prospective controlled study. The main group, who received both traditional treatment and genetic therapy, consisted of 74 patients. The rest 60 patients were included into the control group. Of 74 patients from the main group, genetic therapy was used together with conservative means in 39 patients and with reconstructive vascular operations in 35 patients. The gene-engineering angiogenesis stimulation therapy proved to be effective and safe. The combination of angiogenesis genetic stimulation with reconstructive vascular surgery demonstrated significantly better results, then monotherapy.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inducing Agents; Chronic Disease; Female; Follow-Up Studies; Genetic Therapy; Humans; Ischemia; Leg; Male; Middle Aged; Neovascularization, Pathologic; Prospective Studies; Ribonuclease, Pancreatic; Treatment Outcome; Vascular Surgical Procedures

The authors have studied therapeutic outcomes in a total of 38 patients diagnosed with occlusions of the femoropopliteal segment. In the Study Group patients (n = 19), the operation of femoropopliteal bypass grafting was supplemented by using gene stimulators of angiogenesis (gene constructions with the genes of vascular endothelial growth factor, and angiogenin). The Control Group patients (n = 19) were subjected to a reconstructive vascular operation alone. The remote results were followed up from six to twenty-six months, having shown reliably better therapeutic outcomes obtained in the Study Group patients, as judged by the distance of pain-free walking, the time of restoration of the baseline parameters of blood flow during the treadmill test, muscular perfusion, and the quality of life indices. A conclusion was made that the use ofangiogenesis-stimulating methods combined with reconstructive vascular operations improves the long-term outcomes in patients presenting with lower limb chronic ischaemia.

Topics: Aged; Angiogenesis Inducing Agents; Blood Vessel Prosthesis; Chronic Disease; Drug Therapy, Combination; Exercise Test; Female; Follow-Up Studies; Guideline Adherence; Humans; Injections, Intramuscular; Ischemia; Leg; Male; Middle Aged; Neovascularization, Physiologic; Quality of Life; Ribonuclease, Pancreatic; Time Factors; Tissue Engineering; Treatment Outcome; Vascular Endothelial Growth Factor A; Vascular Surgical Procedures

Inflammatory bowel disease (IBD) is a poorly understood chronic immune disorder for which there is no medical cure. Milk and colostrum are rich sources of bioactives with immunomodulatory properties. Here we compared the therapeutic effects of oral delivery of bovine milk-derived iron-saturated lactoferrin (Fe-bLF), angiogenin, osteopontin (OPN), colostrum whey protein, Modulen IBD (Nestle Healthsciences, Rhodes, Australia), and cis-9,trans-11 conjugated linoleic acid (CLA)-enriched milk fat in a mouse model of dextran sulfate-induced colitis. The CLA-enriched milk fat significantly increased mouse body weights after 24d of treatment, reduced epithelium damage, and downregulated the expression of proinflammatory cytokines and nitrous oxide. Modulen IBD most effectively decreased the clinical score at d 12, and Modulen IBD and OPN most effectively lowered the inflammatory score. Myeloperoxidase activity that denotes neutrophil infiltration was significantly lower in mice fed Modulen IBD, OPN, angiogenin, and Fe-bLF. A significant decrease in the numbers of T cells, natural killer cells, dendritic cells, and a significant decrease in cytokine expression were observed in mice fed the treatment diets compared with dextran sulfate administered mice. The Fe-bLF, CLA-enriched milk fat, and Modulen IBD inhibited intestinal angiogenesis. In summary, each of the milk components attenuated IBD in mice, but with differing effectiveness against specific disease parameters.

Topics: Animals; Australia; Chronic Disease; Colitis; Colostrum; Cytokines; Dairy Products; Dextran Sulfate; Disease Models, Animal; Glycolipids; Glycoproteins; Lactoferrin; Linoleic Acids, Conjugated; Lipid Droplets; Male; Mice; Mice, Inbred BALB C; Milk; Milk Proteins; Nitrous Oxide; Osteopontin; Ribonuclease, Pancreatic; Whey Proteins

A reciprocal link between inflammation, oxidative/nitrosative stress, and endothelial dysfunction has been postulated in chronic heart failure (CHF). The endothelial repair mechanisms involved remain to be determined. Our aim was to investigate whether there are detectable signs of ongoing angiogenesis in serum of CHF patients and to evaluate the correlation with indexes of haemodynamic and functional impairment.. Enzyme-linked immunosorbent assay tests were used to quantify angiogenin, angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, Tie-2, and brain natriuretic peptide in serum of 87 patients with CHF of increasing severity according to New York Heart Association (NYHA; class I, n = 8; II, n = 45; and III, n = 34) and in 14 healthy subjects matched for age and sex. Angiogenin, angiopoietin-2, and Tie-2 were significantly increased in CHF of increasing severity (Kruskal-Wallis: p = 0.0004, p < 0.0001, and p = 0.017, respectively). Angiopoietin-2 was inversely correlated with the 6-min walking test (r = -0.65, p < 0.0001), peak oxygen consumption (VO(2max); r = -0.57, p = 0.0002), and deceleration time (r = -0.61, p < 0.0001). Multiple regression analysis showed that angiopoietin-2 was mainly associated with VO(2max) (p = 0.018). The angiopoietin-2 area under the receiver operating characteristic curve for CHF diagnosis was 0.94 (95% CI 0.88-0.99; p < 0.001).. These data demonstrate that angiopoietin-2 and selected serum markers of angiogenesis progressively increase with haemodynamic and functional decline in CHF.

Topics: Aged; Analysis of Variance; Angiopoietin-1; Angiopoietin-2; Biomarkers; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Hemodynamics; Humans; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Oxygen Consumption; Peptide Fragments; Receptor, TIE-2; Regression Analysis; Ribonuclease, Pancreatic; Severity of Illness Index; Stroke Volume; Up-Regulation; Vascular Endothelial Growth Factor A; Ventricular Function, Left

The article contains experimental data on angiogenesis stimulated by plasmid containing the angiogenin gene. After the introduction of the gene construction, the number of capillars in the chorion-allantois membrane increases 2 to 3 times; in an ischemized limb of a rat it increases by 20 to 30%. Intramuscular administration of genetic engineering construction to patients with chronic lower limb ischemia improved the patients' condition, consisting in an increase in painless walking distance and ankle-brachial index, as well as in trophic defect healing and the betterment of muscular perfusion. Positive effects were noted after 2 to 4 weeks of treatment and remained during 6 to 24 months. There were no side-effects, except low grade fever during 1 to 2 days.

Topics: Adenoviridae; Adult; Aged; Animals; Chick Embryo; Chronic Disease; Data Interpretation, Statistical; Disease Models, Animal; Female; Fibroblast Growth Factors; Follow-Up Studies; Genetic Engineering; Genetic Vectors; Humans; Ischemia; Leg; Male; Middle Aged; Neovascularization, Physiologic; Plasmids; Rats; Rats, Wistar; Ribonuclease, Pancreatic; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A

Accumulated evidence suggests that myogenesis and angiogenesis induced by implanted cells play important roles in restoring cardiac function after a myocardial infarction. The current study investigated the effects of transplanted autologous mesenchymal stem cells overexpressing angiogenin on myocardial perfusion and cardiac function in the porcine chronic ischemic model.. Chronic ischemia was generated in Yorkshire pigs by placing an ameroid constrictor around the left circumflex artery. Four weeks after occlusion, the animals were randomly separated into 4 groups: pigs in the MSC(AdAng) or MSC(AdNull) groups were implanted with 6 x 10(8) mesenchymal stem cells infected with adenovirus containing angiogenin gene or null adenovirus, respectively; pigs in the AdAng or AdNull groups were injected intramyocardially with adenovirus (5 x 10(9) plaque forming unit/pig) containing angiogenin gene or null adenovirus, respectively. Four weeks after implantation, mesenchymal stem cells prelabeled with DiI were observed within the implanted area in both cell transplantation groups.. Angiogenin protein levels were significantly greater in the MSC(AdAng) and AdAng groups than in the other 2 groups and were associated with greater neovessel formation than in the other 2 groups. Mesenchymal stem cell transplantation decreased scar size and increased scar thickness. Both the AdAng and MSC(AdNull) groups experienced improved cardiac function compared with that seen in the AdNull group. However, a synergistic effect of mesenchymal stem cells and angiogenin was observed in the MSC(AdAng) group because myocardial perfusion and cardiac function increased significantly (P < .05 for all groups) in this group compared with all the others.. Transplantation of autologous mesenchymal stem cells transfected with the angiogenin gene revealed a synergistic effect on the improvement of heart perfusion and function after ameroid occlusion.

Topics: Animals; Cells, Cultured; Chronic Disease; Disease Models, Animal; Gene Expression Regulation; Mesenchymal Stem Cells; Myocardial Ischemia; Ribonuclease, Pancreatic; Stem Cell Transplantation; Swine

Angiogenesis is critical for the clinical progression of haematopoietic malignancies and depends on angiogenic factors. Angiogenin is a powerful factor produced by neoplastic cells and host microenvironment. High levels of soluble angiogenin (sAng) correlate with a poor prognosis in patients affected by acute myeloid leukaemia and myelodysplastic syndromes, but no data are available on sAng in chronic myeloproliferative disorders (CMD). Therefore, in this study we investigated the clinical significance of the angiogenin in sera of patients with chronic myeloid leukaemia (CML) (n = 14) or essential thrombocythaemia (ET) (n = 20), and correlated them with those of soluble transforming growth factor-beta(1) (sTGF beta(1)). Enzyme-linked immunosorbent assay detected (P < 0.05) higher levels of sAng in CMD compared with healthy subjects (1026.74 +/- 464.60 pg/mL and 196.00 +/- 39.90 pg/mL, respectively). The highest levels of sAng were detected in CML patients (1349.23 +/- 549.55 pg/mL). Interestingly, CML patients who achieved haematological remission after interferon therapy showed circulating levels of angiogenin significantly (P < 0.05) decreased when compared with those at diagnosis. In ET patients, levels of angiogenin (889.34 +/- 267.66 pg/mL) and sTGF beta(1) (76.69 +/-6.08 pg/mL) were higher (P < 0.05) compared with healthy controls (57.93 +/- 19.39 pg/mL). No correlation was found between levels of sAng and levels of sTGF beta(1) or platelet count among ET patients. Our results show for the first time that elevated blood levels of angiogenin feature chronic myeloid malignancies, suggesting a role of angiogenin in the pathogenesis of these diseases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Chronic Disease; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Myeloproliferative Disorders; Neoplasm Proteins; Prognosis; Remission Induction; Ribonuclease, Pancreatic; Solubility; Thrombocythemia, Essential; Transforming Growth Factor beta

The paper presents a new approach to management of lower limb critical ischemia which implements recent advances in molecular biology and genetic engineering technologies. A new original compound incorporating angiogenin gene was developed to activate neoangiogenesis processes after injection into living tissues. Experimental data evidence a potential efficacy of new method for complex management of critical ischemia.

Topics: Animals; Chick Embryo; Chronic Disease; DNA, Recombinant; Genetic Vectors; Ischemia; Lower Extremity; Male; Neovascularization, Physiologic; Plasmids; Protein Engineering; Rats; Rats, Wistar; Ribonuclease, Pancreatic; Vascular Surgical Procedures

We previously demonstrated the increased expression of angiogenin (ANG) in pancreatic cancer and its relation to cancer aggressiveness; however, the expression patterns and the roles of angiogenin in chronic pancreatitis are still unknown. We investigated the expression of ANG both in the tissues and in the sera of chronic pancreatitis patients (pure chronic pancreatitis) by using in situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay. In situ hybridization revealed no detectable ANG messenger RNA (mRNA) signals in all tissues of pure chronic pancreatitis and normal pancreas. Only a small amount of protein band expression was obtained in all of the protein lysates of pure chronic pancreatitis and normal pancreas. Accordingly, there was no significant difference between the mean serum ANG concentration of chronic pancreatitis patients (352.1+/-72.5 ng/ml) and that of healthy volunteers (357.6+/-45.2 ng/ml). By contrast, acinar cells and interstitial fibroblasts in the tissues surrounding pancreatic cancer showed increased ANG mRNA expression. Strong protein band expression was obtained in the protein lysates of pancreatic cancer surrounding tissue, and mean serum ANG concentration was increased in pancreatic cancer patients. These findings suggest that ANG expression is increased in pancreatic cancer surrounding tissue but is not increased in pure chronic pancreatitis, and that ANG is potentially involved in the pancreatic cancer microenvironment rather than the establishment of pure chronic pancreatitis.

Topics: Blotting, Western; Chronic Disease; Gene Expression; Humans; In Situ Hybridization; Pancreatic Neoplasms; Pancreatitis; Proteins; Reference Values; Ribonuclease, Pancreatic; RNA, Messenger