angiogenin and Diabetes-Mellitus--Type-1

To determine if early pregnancy serum biomarkers in high-risk women who develop preeclampsia vary according to risk factor.. We performed a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in high-risk women. Serum biomarker levels at enrollment (before initiation of aspirin or placebo) were compared between women who did and did not develop preeclampsia, both for the group as a whole and within each of 4 high-risk groups (insulin-dependent diabetes, hypertension, multiple gestation, and previous preeclampsia) using a regression model adjusting for gestational age at collection and prepregnancy body mass index.. 1258 women were included (233 with insulin-dependent diabetes, 387 with chronic hypertension, 315 with a multiple gestation, 323 with previous preeclampsia). Multiple early pregnancy serum biomarkers differed between women who did and did not develop preeclampsia. Each high-risk group had a unique and largely nonoverlapping pattern of biomarker abnormality. Differences between those who did and did not develop preeclampsia were noted in vascular cell adhesion molecule in the diabetes group; human chorionic gonadotropin, soluble tumor necrosis factor receptor-2, tumor necrosis factor-alpha, selectin and angiogenin in the chronic hypertension group; interleukin-6, placental growth factor, soluble fms-like tyrosine kinase plus endoglin to placental growth factor ratio in the multiple gestation group; and angiogenin in the previous preeclampsia group.. Patterns of serum biomarkers vary by high-risk group. These data support the hypothesis that multiple pathogenic pathways lead to the disease recognized clinically as preeclampsia.

Topics: Adult; Antigens, CD; Biomarkers; Chorionic Gonadotropin; Diabetes Mellitus, Type 1; Endoglin; Female; Humans; Hypertension; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Pregnancy Proteins; Pregnancy, Multiple; Progesterone; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor, Type II; Ribonuclease, Pancreatic; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-1; Young Adult

Our previous studies have found that bone-marrow-stromal cells (BMSC) therapy improves functional recovery after stroke in non-diabetic rats while increases brain hemorrhage and induces arteriosclerosis-like changes in type-one-diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats.. T1DM-rats induced by streptozotocin were subjected to 2 hours of middle-cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5×10(6)); 3) Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5×10(6)) +Niaspan (40 mg/kg, daily for 14 days) combination starting at 24 hours after MCAo. All rats were monitored for 14 days.. Combination BMSC+Niaspan treatment of T1DM-MCAo rats did not increase brain hemorrhage, and significantly decreased BBB leakage and vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal-carotid-artery compared to non-treatment control and BMSC monotherapy animals.. Combination therapy using BMSC with Niaspan decreases BBB leakage and cerebral arteriosclerosis-like changes. These beneficial effects may be attributed to the decreased expression of Angiogenin, MMP9 and ED1.

Topics: Animals; Blood-Brain Barrier; Diabetes Mellitus, Type 1; Disease Models, Animal; Ectodysplasins; Intracranial Arteriosclerosis; Male; Matrix Metalloproteinase 9; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Niacin; Permeability; Protein Binding; Protein Transport; Rats; Ribonuclease, Pancreatic; Stroke; Stroke Rehabilitation

Angiogenin levels are increased in children and adolescent patients with type 1 diabetes, regardless of the extent of diabetic microangiopathy. However, little is known about the angiogenin concentrations in adults with type 1 diabetes. Thus we studied its level in middle aged subjects with the presence of diabetic nephro-, retino and neuropathy.. We investigated the data of 57 (age 39±6.6 years, 45.6% of males) patients with type 1 diabetes and 38 age-matched control subjects without diabetes (age 37.1±5.9 years, 42.1% of males), including medical histories, evidences of microangiopathy and serum angiogenin concentrations.. Serum angiogenin level was lower in patients with type 1 diabetes [384.2(190.4-999.8) ng/ml] compared to controls [460.4(230.6-708.2) ng/ml], p=0.04. In patients with overt diabetic nephropathy the angiogenin level was higher when compared to patients without nephropathy [568.2(269.6-999.8) vs 369.4(190.4-999.8) ng/ml, p=0.01]. There were no differences between angiogenin levels in subgroups of patients distinguished by the presence of other microvascular complications or other concomitant vascular risk factors despite cigarette smoking [smokers: 516.2(294.4-999.8) vs. non-smokers: 372.1(190.4-924.8) ng/ml, p=0.01].. Regardless of the presence of diabetic microangiopathy, angiogenin level in middle-aged type 1 diabetes patients is lower than in controls. The presence of overt nephropathy and smoking habit in middle-aged patients with type 1 diabetes are associated with higher angiogenin level.

Topics: Adult; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Gene Expression Regulation; Glomerular Filtration Rate; Humans; Male; Neovascularization, Pathologic; Ribonuclease, Pancreatic

Diabetic retinopathy is the most common cause of vision loss in young adults in developed countries. The disease therapy with anti-vascular endothelial growth factor (VEGF) agents gives some positive results, but is associated with retinal ischemia and vasoconstriction. Therefore, determination of factors involved in the physiological and pathological angiogenesis in the diabetic eye is of great importance for understanding of the pathogenesis of diabetic retinopathy and its effective treatment. Previously, we found that diabetic patients were characterized by increased serum concentration of VEGF, but decreased levels of other proangiogenic factor-angiogenin. The involvement of VEGF in pathogenesis of diabetic retinopathy is well established, but there is lack of data regarding angiogenin in retinopathy. Therefore, in the present study we measured angiogenin concentration in vitreous and serum samples of the patients with type 1 diabetes to determine its role in diabetic retinopathy. In addition, in each time, we compared the level of angiogenin with level of VEGF as a known factor involved in the pathogenesis of the disease. Angiogenin was found to be significantly more abundant in serum than in vitreous in both diabetic groups. In addition, patients with retinopathy had twofold lower vitreous angiogenin levels than diabetic individuals without complications. On the contrary, vitreous concentration of VEGF was dramatically increased only in participants with retinopathy. Patients without diabetic complications had significantly lower VEGF levels in vitreous than in serum and were characterized by high local and systemic concentration of angiogenin. These data suggest a local imbalance between two proangiogenic factors-VEGF and angiogenin in retinopathy. Low vitreous concentration of angiogenin in diabetic patients suggests that this factor is not responsible for pathological neovascularization in diabetic eye. Further studies will elucidate if angiogenin can be used to improve the insufficient angiogenesis in diabetes and prevent retinal ischemia after retinopathy treatment with anti-VEGF agents.

Topics: Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Vitreoretinal Surgery; Vitreous Body

Diabetes alters microvascular structure and function and is a major risk factor for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis and reduced VEGF-A expression have been observed, whereas in healthy muscle exercise is known to have opposite effects. We studied the effects of type 1 diabetes and combined exercise training on angiogenic mRNA expression and capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses showed that diabetes altered the expression of several genes involved in angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1, VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospondin-1 and retinoblastoma like-2 were increased. Exercise training alleviated some of these changes, but could not completely restore them. VEGF-A protein content was also reduced in diabetic muscles. In line with the reduced levels of VEGF-A and other angiogenic factors, and increased levels of angiogenesis inhibitors, capillary-to-muscle fiber ratio was lower in diabetic mice compared to healthy controls. Exercise training could not restore capillarization in diabetic mice. In conclusion, these data illustrate that type 1 diabetes is associated with reduced skeletal muscle capillarization and the dysregulation of complex angiogenesis pathways.

Topics: Angiogenesis Inducing Agents; Animals; Capillaries; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Disease Models, Animal; Gene Expression Regulation; Male; Mice; Mice, Inbred Strains; Muscle, Skeletal; Neovascularization, Pathologic; Neovascularization, Physiologic; Physical Conditioning, Animal; Ribonuclease, Pancreatic

We evaluated the concentrations of vascular endothelial growth factor (VEGF) and angiogenin in the umbilical cord blood from 14 fetuses with erythroblastosis or alloimmune thrombocytopenia and at birth from 28 preterm fetuses, from 42 healthy term fetuses, and from 24 term fetuses born to mothers with insulin-treated diabetes. A correlation appeared between VEGF and angiogenin levels (r = 0.44, p = 0.038). The gestational age correlated with both VEGF (r = 0.38, p = 0.0008) and angiogenin levels (r = 0.80, p = 0.0001). The concentration of VEGF was lower in fetuses born to mothers with insulin-treated diabetes than in the healthy term fetuses (p = 0.0028), but this difference was absent for angiogenin (p > 0.05). In conclusion, in umbilical cord plasma, a developmental increase was evident in concentrations of VEGF and angiogenin during the last trimester of gestation. That the umbilical cord VEGF level was lower in term fetuses born to mothers with diabetes than in term fetuses of healthy mothers may be associated with an aberrant fetal vascular development in diabetic pregnancies.

Topics: Diabetes Mellitus, Type 1; Embryonic and Fetal Development; Erythroblastosis, Fetal; Erythropoietin; Female; Fetal Blood; Gestational Age; Humans; Insulin; Isoantibodies; Male; Pregnancy; Pregnancy in Diabetics; Ribonuclease, Pancreatic; Thrombocytopenia; Vascular Endothelial Growth Factor A

Angiogenin serum levels were measured in a large group of type 1 diabetic young patients, looking at whether increased Angiogenin concentrations are associated with long-term glycemic control and microvascular complications.. Four groups of patients were compared to 223 age- and sex- matched healthy controls: 196 type 1 diabetic patients (age range 3-24 years, onset of diabetes before the age of 12 years; duration of disease longer than 2 years), without microvascular complications were divided into three groups on the basis of age (group 1, n = 37, age < 6 years; group 2, n = 71, age 6-12 years; group 3, n = 88, age > 12 years); 53 adolescents and young adults (age 16.1-29.7 years) with diabetic microvascular complications (background, preproliferative or proliferative retinopathy, albumin excretion rate 20-200 microg min-1) (group 4).. Angiogenin serum levels were significantly increased in diabetic pre-school and pre-pubertal children, and particularly elevated in pubertal subjects compared with age- and sex-matched controls. Adolescents and young adults with microvascular complications had very high angiogenin concentrations. One-year mean HbA1c values were correlated with angiogenin levels (r = 0.389; p < 0.01). In poorly controlled diabetics (HbA1c > 10%), long-term (2 years) improvement of glycemic control determined a significant reduction of angiogenin concentrations in both pre-school and pre-pubertal children as well as in pubertal youngsters.. Angiogenin serum concentrations are increased in diabetic children even before puberty. Severity of microvascular complications is associated with markedly increased angiogenin serum levels. Long-term tight glycemic control determines a consistent reduction of angiogenin concentrations.

Topics: Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Male; Ribonuclease, Pancreatic

Microangiopathy, one of the most important complications of diabetes mellitus in humans, is associated with increased angiogenic response and proliferative lesions in various organs. Angiogenin, a polypeptide with a molecular size of 14 kD, is a potent inducer of vascular growth. This study aimed at investigating whether serum angiogenin levels are elevated in children and adolescents (youngsters) with insulin-dependent diabetes mellitus and whether angiogenin levels are affected by duration and metabolic control of the disease. It is assumed that angiogenin levels reflect the increased angiogenesis associated with microangiopathy, whether clinically evident or not. Forty diabetic youngsters were compared with 30 healthy control subjects (mean age +/- SD, 14.3 +/- 3.6 y and 13.8 +/- 3.6 y, respectively). The patients' disease duration and glycosylated Hb were (mean +/- SD) 6.2 +/- 3.8 y and 9.6 +/- 1.8%, respectively. Angiogenin (ng/mL) was measured in serum samples by an enzyme immunoassay and was found to be significantly higher (mean +/- SE) in patients (353.3 +/- 20.0) than in control subjects (244.7 +/- 9.6) (p = 0.0002). Levels did not vary with age, but were significantly higher in females compared with male subjects (p = 0.01). In the diabetic youngsters no significant differences were noticed with respect to duration or metabolic control of the disease. In conclusion, serum angiogenin levels were found to be increased among diabetic youngsters, irrespective of the duration and metabolic control of the disease, as well as in female subjects, with or without diabetes.

Topics: Adolescent; Adult; Albuminuria; Angiogenesis Inducing Agents; Biomarkers; Blood Pressure; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Male; Proteins; Reference Values; Ribonuclease, Pancreatic