Disease relevance of Diabetic Angiopathies

• Because diabetic vascular disease is accompanied by a state of hypercoagulability, manifested by increased thrombin activity and foci of intravascular coagulation, we investigated whether a specific procoagulant property of the endothelium--production and surface expression of tissue factor--is modified by elevated glucose concentrations [1].
• Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women) [2].
• These results show that blood pressure in insulindependent diabetes mellitus is sodium sensitive, but that this is not related to the nonmodulator phenotype, and suggest that in IDDM a relatively high sodium intake may be a factor that predisposes to the development of diabetic vascular disease [3].
• Analysis of the published data, results of the muscle biopsies, and a technetium-99m sestamibi scan suggest that the condition, which occurs against a background of diabetic microangiopathy, can be triggered by an ischaemic event and causes extensive muscle necrosis through hypoxia-reperfusion injury and compartment syndrome [4].
• In order to investigate the relationship between urinary excretion of sialic acid and the severity of diabetic microangiopathy, urinary levels of sialic acid were determined in patients with non-insulin-dependent diabetes mellitus [5].

High impact information on Diabetic Angiopathies

• A similar mechanism involving methylglyoxal-modification of other coregulator proteins may play a role in the pathobiology of a variety of conditions associated with changes in methylglyoxal concentration, including cancer and diabetic vascular disease [6].
• Our observations suggest that glycoxidation reactions in the arterial microenvironment contribute to early diabetic vascular disease, raising the possibility that antioxidant therapies might interrupt this process [7].
• Nitric oxide from the vascular endothelium contributes to the control of normal vascular tone, and endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disease [8].
• 15-Hydroxy-5,8,11,13-eicosatetraenoic acid inhibits human vascular cyclooxygenase. Potential role in diabetic vascular disease [9].
• Blockade of chlorpropamide-alcohol flushing by indomethacin suggests an association between prostaglandins and diabetic vascular complications [10].

Chemical compound and disease context of Diabetic Angiopathies

• Prospective studies on the effect of therapeutic agents such as acetylsalicylic acid on the natural course of diabetic vascular disease are indicated [11].
• Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis [12].
• Because increased TXA2 production of diabetic platelets is thought to play an important pathogenetic role in diabetic angiopathy, we conclude that vitamin E treatment could be beneficial with respect to platelet-vessel-wall interaction and thus might be promising for the prevention of diabetic angiopathy [13].
• Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan [14].
• These results demonstrate that aminoguanidine inhibits NO. production and suggest a role for NO. in the pathogenesis of diabetic vascular complications [15].

Biological context of Diabetic Angiopathies

• Since beta-thromboglobulin is a platelet-specific protein the results indicate that diabetic microangiopathy is associated with evidence of platelet activation and that this may be influenced by the degree of biochemical control [16].
• These studies indicate that events other than activation of protein kinase C or A bridge high ambient glucose to changes in endothelial cell gene expression that may contribute to diabetic angiopathy [17].
• Haptoglobin genotype and diabetic microangiopathies in Japanese diabetic patients [18].
• Increased expression of vascular endothelial growth factor (VEGF) has been correlated with increased oxidative stress and formation of peroxynitrite in numerous disease conditions, including diabetic microangiopathy, tumor angiogenesis, and atherosclerosis [19].
• The antioxidant action of troglitazone, which is attributable to the similarity of its molecular structure to that of alpha-tocopherol, may be of benefit in preventing diabetic vascular complications, in addition to having hypoglycemic and hypolipidemic effects [20].

Anatomical context of Diabetic Angiopathies

• Growing evidence that high glucose may be a causative agent of the thickened vascular basement membranes that characterize diabetic microangiopathy prompted this investigation of the underlying mechanisms [21].
• In BB/W diabetic rats and in rats with SS-D, indices of IAP were significantly increased in tissues and vessels predisposed to diabetic vascular disease in humans, including the eyes (anterior uvea, posterior uvea, and retina), sciatic nerve, aorta, kidney, and new vessels formed after induction of diabetes [22].
• In target tissues of diabetic vascular complications, such as the endothelium and mesangium, galectin-3 is weakly expressed under basal conditions and is markedly upregulated by the diabetic milieu (and to a lesser extent by aging) [23].
• Troglitazone might be useful for diabetic angiopathy, including nephropathy and coronary artery disease [24].
• These results show that high glucose concentration activates endothelial cells leading to monocytes adhesion providing further evidence that hyperglycaemia might be implicated in vessel wall lesions contributing to diabetic vascular disease [25].

Gene context of Diabetic Angiopathies

• This spectrum of pathological changes is reminiscent of diabetic microangiopathy, suggesting that the endothelium-restricted Pdgfb knockouts may serve as models for some of the pathogenic events of vascular complications to diabetes [26].
• The results suggest that AGE can elicit angiogenesis through the induction of autocrine vascular VEGF, thereby playing an active part in the development and progression of diabetic microangiopathies [27].
• LAP has an important function in the latency of TGF-beta complex, but the role of LTBP-1 is not known in diabetic angiopathy [28].
• Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations [29].
• Role of endothelin in diabetic vascular complications [30].

Analytical, diagnostic and therapeutic context of Diabetic Angiopathies

• 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes [31].
• Serum levels of both laminin, a glycoprotein in the basement membrane, and type III procollagen peptide (P-III-P) were measured by specific radioimmunoassays according to the methods of Brocks et al. and Rohde et al. respectively and analyzed with regard to diabetic microangiopathy, glycemic control, diabetic duration and treatment [32].
• Ticlopidine has also been used to prevent occlusion and improve patency of aortocoronary bypass grafts, to prevent ischemic ulcers in patients with chronic arterial occlusive disease, and to slow the progression of diabetic microangiopathy [33].
• The relationship between plasma fibronectin and changes of blood rheology may be important for the occurrence and progression of diabetic microangiopathy [34].
• We suggest that serum NAG activity, E-selectin, and ICAM-1 concentrations may be used together with laser-Doppler flowmetry in Type 1 diabetic patients as early indicators of vascular changes in very early stage of diabetic microangiopathy [35].

References