6-ketoprostaglandin-f1-alpha and Diabetic-Angiopathies

Although many data regarding the biosynthesis of thromboxane A2 and prostacyclin in diabetes mellitus have recently appeared in the literature, it is not clear whether an imbalance between the generation of the two prostaglandins might be connected to the vascular complications of diabetes. In the present review we have tried to emphasize the most significant aspects of these studies and we have focused on alterations of platelet prostacyclin receptors and on the effects of circulating immune complexes on platelets of diabetics. It is likely that studies on the release of platelet derived growth factor as well as more precise definitions of its action on vessel wall cells leading to a massive release of prostacyclin, will permit us to ascertain whether an alteration in prostaglandin ratio is linked to the genesis of the vascular complications in diabetics.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antigen-Antibody Complex; Blood Platelets; Blood Vessels; Cyclic AMP; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Endothelium; Epoprostenol; Humans; Models, Biological; Platelet Aggregation; Platelet-Derived Growth Factor; Receptors, Cell Surface; Receptors, Epoprostenol; Receptors, Platelet-Derived Growth Factor; Receptors, Prostaglandin; Thromboxane A2; Thromboxane B2

To investigate the relationship between syndrome differentiation of traditional Chinese medicine (TCM) and characteristic changes of vascular endothelial function in patients with diabetic arterial occlusion (DAO) of lower extremities.. Forty patients with DAO were selected as trial group. Twenty patients among them were attributed to blood stasis syndrome (group A1), and the others were attributed to syndrome of pathogenic dampness-heat attacking the lower limb (group A2) according to syndrome differentiation type of TCM. Patients with diabetes (group B), arteriosclerosis obliterans (group C) and healthy people (group D) were observed as the control groups, respectively. There were 20 cases in each group. Endothelium-dependent dilation (EDD) and endothelium-independent dilation (EID) were measured by high resolution ultrasound in the 100 subjects and the changes of vascular tension factors were also studied.. The results showed that EDD in group A was reduced significantly as compared with that in the groups B, C and D. The levels of vascular contractile factors such as endothelin-1 (ET-1) and thromboxane B2 (TXB2) in group A were higher than those in the groups B, C and D, while the levels of vascular dilatory factors such as nitric oxide (NO) and 6-keto-prostaglandin F1alpha(6-Keto-PGF1alpha) were declined significantly as compared with those in the groups B and D. Linear correlation analysis showed that EDD was correlated positively with the levels of NO and 6-Keto-PGF1alpha, while the levels of ET-1 and TXB2 had negative correlation with EDD. EDD and EID in group A2 were declined significantly as compared with those in group A1.. Our findings indicate that endothelial dysfunction may play an important role in the pathogenesis of DAO and may be associated with syndrome differentiation of TCM.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Arterial Occlusive Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diagnosis, Differential; Endothelin-1; Endothelium, Vascular; Female; Humans; Lower Extremity; Male; Medicine, Chinese Traditional; Middle Aged; Nitric Oxide; Thromboxane B2

To study the change of vascular tension factors (VTF), including vascular contractile factors as endothelin-1 (ET-1), thromboxane A2 (TXA2) and vascular dilatory factors as nitric oxide (NO), prostacyclin (PGI2), in different stage of peripheral diabetic arterial occlusion (PDAO), and to preliminarily explore the clinical significance of these changes.. VTF in 40 diabetic patients, 15 of 2nd stage and 25 of 3rd stage, were observed by measuring level of ET-1, NO, TXB2 and 6-keto-PGF1alpha in blood plasma with RIA assay.. (1) ET-1 and TXB2 levels in all patients were higher than those in control (P < 0.05 and P < 0.01), those in patients of 3rd stage was higher than those of 2nd stage, showing significant difference (P < 0.05). (2) NO and 6-keto-PGF1alpha levels in all patients was lower than those in control, but showed no significant difference between patients of various stages (P > 0.05).. There are changes of VTF in patients with PDAO, manifesting as increase of vascular contractive factors and decrease of vascular dilative factor. The changes are diffrent in various stages, the vascular contractive and thrombotic factors in patients of 3rd stage are higher than those in patients of 2nd stage, but the injury on vascular dilative factors in the two stages showed insignificant difference.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelin-1; Epoprostenol; Female; Humans; Lower Extremity; Male; Middle Aged; Nitric Oxide; Thromboxane A2; Thromboxane B2; Vasomotor System

We analyzed the in vitro effects of sorbitol and fructose on platelet function. Sorbitol and fructose increased platelet aggregation induced with adenosine diphosphate (ADP) or collagen in whole blood, but had no effect in platelet-rich plasma. The concentration that increased basal aggregation by 50% with ADP as the inducer was 12.89 +/- 1.55 mmol/L for fructose, and 18.99 +/- 2.01 mmol/L for sorbitol. When collagen was the inducer, these concentrations were 15.02 +/- 0.98 mmol/L for fructose, and 12.94 +/- 1.57 mmol/L for sorbitol. Both sugars increased, in a concentration-dependent way, the proaggregatory effect of erythrocytes, and erythrocyte uptake of adenosine. Time to uptake of 50% adenosine was 2.1 +/- 0.3 min in control samples, 0.14 +/- 0.01 min in the presence of fructose, and 0.23 +/- 0.03 min with sorbitol. Both sugars reduced vascular prostacyclin synthesis, with 50% inhibitory concentrations of 26.48 +/- 1.97 mmol/L for fructose, and 39.53 +/- 2.81 mmol/L for sorbitol. Both sugars also increased arterial lipid peroxidation by 30% (sorbitol) and 23% (fructose). We conclude that these two sugars enhance platelet function and disrupt the thromboxane/prostacyclin ratio.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine; Adenosine Diphosphate; Adult; Animals; Aorta; Blood Glucose; Blood Platelets; Collagen; Diabetic Angiopathies; Epoprostenol; Erythrocytes; Fructose; Humans; Hyperglycemia; In Vitro Techniques; Lipid Peroxidation; Male; Platelet Activation; Platelet Aggregation; Rats; Rats, Wistar; Sorbitol; Thromboxane B2

We studied the effects of glycated lipoproteins of low- and high-density (LDL and HDL) on platelets and vascular endothelial cells. After pretreatment for 5 minutes at 37 degrees C, the thrombin-induced synthesis of thromboxane B2 in washed platelets was significantly increased by glycated LDL as compared with native LDL (198.9 +/- 16.2 vs 90.3 +/- 29.4 ng/10(9) platelets, n = 8, p less than 0.01). Platelet aggregation was also increased by glycated LDL as compared with native LDL. After treatment with platelet-rich plasma for 5 hours at 37 degrees C, these values were suppressed by native HDL vs the control (buffer), but not by glycated HDL. Abnormalities in the release of 6-keto prostaglandin F1 alpha and lactate dehydrogenase from vascular endothelial cells were also induced by glycated LDL and/or HDL. These observations suggest that abnormalities induced in platelets and vascular endothelial cells by glycated lipoproteins may play an important role in the development of atherosclerosis in patients with diabetes mellitus.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Blood Platelets; Diabetic Angiopathies; Dinoprostone; Endothelium, Vascular; Female; Glycation End Products, Advanced; Glycosylation; Humans; In Vitro Techniques; Lipoproteins, HDL; Lipoproteins, LDL; Male; Platelet Aggregation; Thromboxane B2

A decrease in the vitamin E content of human diabetic platelets is closely associated with the accelerated platelet aggregation and platelet prostaglandin metabolism seen in patients with diabetes mellitus. We investigated the effect of vitamin E supplementation on these abnormalities of physiological function and prostaglandin metabolism in 14 non-insulin dependent diabetics with proliferative retinopathy. ADP-induced platelet aggregation was inhibited in vitro by the addition of vitamin E in a dose-dependent manner. However, in lower concentrations considered to be physiological doses in vivo, significantly greater inhibition was observed in diabetic platelets than in the control platelets. Next, alpha-tocopheryl nicotinate was administered to diabetics at a daily dose of 600 mg. The platelet vitamin E content was restored to control levels in 13 of the 14 patients after 2-4 weeks of daily administration. The ADP-induced platelet aggregation rate, platelet thromboxane B2 (TXB2, a stable metabolite of TXA2, a vasoconstrictor production, and plasma TXB2 level were low in all 14 diabetics. In contrast, plasma 6-keto-PGF 1 alpha (a stable metabolite of PGI2, a vasodilator) was significantly increased and therefore the 6-keto-PGF 1 alpha/TXB2 ratio in plasma was restored to within normal limits. These results indicate that vitamin E may improve platelet function and prostaglandin metabolism in diabetes mellitus and may be able to provide further beneficial effects in relation to the development of diabetic vascular complications.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Blood Glucose; Blood Platelets; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Reference Values; Thromboxane B2; Time Factors; Vitamin E

Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TXB2) were measured in 55 diabetics and 30 controls with radioimmunoassay. The correlation between diabetic microangiopathy and the ratio of TXB2 and 6-keto-PGF1 alpha was analysed. Diabetics were divided into three groups according to the change of retina and renal function. Group A, diabetics without microangiopathy; group B, diabetics with slight microangiopathy; and group C, diabetics with severe microangiopathy. The results showed that the ratio of TXB2/6-keto-PGF1 alpha was higher in B and C groups (0.997 +/- 0.31 1.10 +/- 0.25 means +/- S) than in the controls (0.72 +/- 0.17 means +/- S) (P less than 0.01). Group A patients had slightly higher level of the ratio (0.85 +/- 0.20 means +/- S) than the controls but the difference was not significant. The results suggest that the TXB2 and 6-keto-PGF1 alpha imbalance exists only in diabetics with microangiopathy and their imbalance might have more significance in the pathogenesis of diabetic microangiopathy than their individual change.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Thromboxane B2

It has been speculated that platelet activation may contribute to the evolution of vascular complications in patients with Type I diabetes mellitus. To address this hypothesis, we measured the plasma and urinary metabolites of thromboxane, presumably of platelet origin, and of prostacyclin, derived from endothelial cells, in addition to more conventional indexes of platelet function. Urinary excretion of the metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha did not differ between diabetics with or without retinopathy and nondiabetic controls. Furthermore, measurement of platelet granule constituents, the aggregation responses to ADP or arachidonic acid, and levels of serum thromboxane B2 failed to discriminate between the groups. The institution of tight diabetic control with multiple daily injections of insulin failed to alter either urinary metabolite excretion or plasma levels of 11-dehydro-thromboxane B2. Conversely, insulin-induced hypoglycemia failed to alter the concentrations of plasma or urinary thromboxane metabolites in nondiabetic volunteers, despite a mean 60-fold increase in plasma epinephrine. These studies suggest that platelet activation does not precede the development of microvascular complications in patients with Type I diabetes who lack clinical evidence of macrovascular disease and have normal renal function. Furthermore, it is unlikely that platelet activation due to intermittent hypoglycemia contributes to the reportedly accelerated development of retinopathy in such patients, when they are subject to tight diabetic control.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Blood Platelets; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Epoprostenol; Humans; Insulin; Platelet Aggregation; Thromboxane B2; Thromboxanes

Concentrations of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of prostacyclin, were measured by radioimmunoassay before and after 3 min of induced ischemia in 45 diabetics and 23 controls matched for age. In the 45 diabetics, 15 had no vascular complications (group I), 10 had a macroangiopathy (group II), 10 had a microangiopathy (group III) and 10 had both macroangiopathy and microangiopathy (group IV). Plasma levels of 6-keto-PGF1 alpha before forearm ischemia were significantly lower in group IV diabetics than in non-diabetic controls (188 +/- 17 pg/ml and 245 +/- 14 pg/ml, respectively). After 3 min of ischemia, plasma 6-keto-PGF1 alpha concentrations were increased in control subjects by 34% and by 21% in group I diabetics. In group III diabetics as well as diabetics with atherosclerotic vascular lesions (groups II and IV), no significant change was observed after 3 min of ischemia. These results suggest that impaired vessel wall prostacyclin production may to some extent be responsible for the development of diabetic retinopathy and nephropathy as well as atherosclerotic vascular complications.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Diabetic Angiopathies; Female; Forearm; Humans; Ischemia; Male; Middle Aged

Prostacyclin, being a potent vasodilator and platelet aggregation inhibitor, is of interest because of its possible relationship to microangiopathy associated with diabetes and other vascular diseases. Using a radioimmunoassay for the stable product of prostacyclin breakdown (6-keto PGF1 alpha) we have examined the ability of serum from diabetic patients to stimulate prostacyclin production in human endothelial cells. Results in the study of the effects of human serum on prostacyclin production by endothelial cells showed that there was a highly significant difference between diabetics and controls, with diabetic serum causing much lower prostacyclin production from cultured cells. The effect of serum in this study was not dependent on the age or sex of the donor.

Topics: 6-Ketoprostaglandin F1 alpha; Blood Vessels; Cells, Cultured; Culture Media; Diabetes Mellitus; Diabetic Angiopathies; Endothelium; Epoprostenol; Humans

Concentrations of the stable antiaggregatory prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and of the proaggregatory thromboxane A2 metabolite thromboxane B2 were measured by radioimmunoassay in plasma from 53 diabetics. In 33 of these patients the ability of platelets to produce thromboxane B2 during spontaneous clotting was also studied. Plasma 6-keto-PGF1 alpha concentrations were higher (p less than 0.05) in the diabetics (mean 107.7 +/- SE 7.6 ng/l) than in non-diabetic controls matched for age and sex (87.5 +/- 4.7 ng/l), and diabetics with microangiography (n = 28) and higher (p less than 0.01) concentrations (124.3 +/- 10.8 ng/l) than those without microangiography (n = 25; 89.2 +/- 9.3 ng/l). Plasma thromboxane B2 concentrations were also higher (p less than 0.01) in the diabetics (mean 218.5 +/- SE 25.3 ng/l) than in the controls (127.7 +/- 9.8 ng/l), but this increase was not related to microangiography. The ability of platelets to generate thromboxane B2 did not differ between the diabetics (181.4 +/- 16.4 microgram/l) and controls (195.8 +/- 11.8 microgram/l). Platelets of diabetics with microangiopathy or taking oral hypoglycaemic agents (n = 19), however, produced decreased amounts of thromboxane B2 during clotting. Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 were not related to concentrations of glucose, haemoglobin A1, high-density lipoprotein cholesterol, cholesterol, triglycerides, magnesium, or creatinine. These results suggest that in diabetics with microangiopathy a balance between prostacyclin and thromboxane A2 is shifted to dominance by prostacyclin.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Blood Coagulation; Blood Platelets; Diabetes Mellitus; Diabetic Angiopathies; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Thromboxane B2; Thromboxanes