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The protein kinase C (PKC) family consists of at least 12 isoforms that possess distinct differences in structure, substrate requirement, expression and localization. To date, identification of the physiological function of individual PKC isoforms has been restricted by the availability of few agents that inhibit or activate the isoforms with specificity.(More)
Diabetic complications are the major cause of morbidity and mortality in persons with diabetes. Chronic hyperglycemia is a major initiator of diabetic microvascular complications (eg, retinopathy, neuropathy, nephropathy). Glucose processing uses a variety of diverse metabolic pathways; hence, chronic hyperglycemia can induce multiple cellular changes(More)
D iabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20 –74 years. During the first two decades of disease , nearly all patients with type 1 diabetes and Ͼ60% of patients with type 2 diabetes have retinopathy. In the Wisconsin Epidemiologic Study of Diabetic Retinopa-thy (WESDR), 3.6% of younger-onset patients (type 1(More)
Increased intracellular reactive oxygen species (ROS) contribute to vascular disease and pro-atherosclerotic effects of diabetes mellitus may be mediated by oxidative stress. Several ROS-scavenging systems tightly control cellular redox balance; however, their role in hyperglycemia-induced oxidative stress is unclear. A ubiquitous antioxidative mechanism(More)
Increased vascular permeability and excessive neovascularization are the hallmarks of endothelial dysfunction, which can lead to diabetic macular edema and proliferative diabetic retinopathy in the eye. Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization and a known vasopermeability factor in nonocular tissues. In(More)
Fibroblastic proliferation accompanies many angiogenesis-related retinal and systemic diseases. Since connective tissue growth factor (CTGF) is a potent mitogen for fibrosis, extracellular matrix production, and angiogenesis, we have studied the effects and mechanism by which vascular endothelial growth factor (VEGF) regulates CTGF gene expression in(More)
Hyperglycemia can cause vascular dysfunctions by multiple factors including hyperosmolarity, oxidant formation, and protein kinase C (PKC) activation. We have characterized the effect of hyperglycemia on p38 mitogen-activated protein (p38) kinase activation, which can be induced by oxidants, hyperosmolarity, and proinflammatory cytokines, leading to(More)
PURPOSE To determine the mechanistic role for adenosine and adenosine receptors in the hypoxic induction of vascular endothelial growth factor (VEGF) in retinal microvascular cells. METHODS Bovine retinal capillary endothelial cells and microvascular pericytes were studied under normoxic (95% air, 5% CO2) or hypoxic conditions (0% to 2% O2, 5% CO2, 93% to(More)
Recent studies have identified that the activation of protein kinase C (PKC) and increased diacylglycerol (DAG) levels initiated by hyperglycemia are associated with many vascular abnormalities in retinal, renal, and cardiovascular tissues. Among the various PKC isoforms, the beta- and delta-isoforms appear to be activated preferentially in the vasculatures(More)
The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely(More)