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Increased free radical activity may contribute to thrombosis via effects on platelet aggregation and the prostanoid balance. To investigate this further we studied 15 Type 1 diabetic patients with retinopathy, matched with uncomplicated Type 1 patients for age, duration of diabetes and HbA1, together with matched healthy non-diabetic control subjects. The oxidative effects of free radicals as total diene conjugates and lipid peroxides were measured, together with redox status extracellularly as plasma albumin-thiols and intracellularly as erythrocyte superoxide dismutase activity. Platelet count, aggregation of platelets in whole blood to collagen, thromboxane B2, and prostacyclin stimulating factor (PGI2SF) were also assessed. Free radicals measured as lipid peroxides were significantly higher (9.6 (8.1-11.6) mumol l-1 (median and interquartile range) in diabetic patients with retinopathy than in control subjects (8.1 (7.4-9.2) mumol l-1; p less than 0.05). There were also significant reductions in redox status both extracellularly as plasma albumin thiols (408 (383-473) vs 490 (456-517) mumol l-1, p less than 0.001) and intracellularly as erythrocyte superoxide dismutase activity (34 (27-41) vs 44 (36-51) g l-1, p less than 0.05) between patients with retinopathy and control subjects. Platelet counts were increased in diabetic patients with retinopathy (p less than 0.05), as was collagen-induced platelet aggregation (p less than 0.01). Prostacyclin stimulating factor was reduced in patients with retinopathy (p less than 0.05) and correlated within the plasma with lipid peroxides (r = -0.53, p less than 0.04) and albumin thiols (r = 0.64, p less than 0.01). The results suggest that diabetic patients, particularly with retinopathy, are under oxidative stress and have an increased thrombotic tendency with increased platelet reactivity and a reduction in prostacyclin stimulating factor.

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Postprandial lipidemia, characterized by high plasma triglyceride-rich lipoprotein remnants, is associated with atherosclerosis. It has also been known that proliferation of vascular smooth muscle cells is crucial for the development of atherosclerosis. In this study, we investigated the direct effect of remnant lipoprotein particles, which consist of chylomicron remnants and very low density lipoprotein remnants, on vascular smooth muscle cell proliferation. Blood was collected from six patients with postprandial lipidemia two hours after their usual meal. Remnant lipoprotein particles were isolated from plasma by immuno-affinity chromatography containing two monoclonal antibodies, anti-apo A-I (H-12) and anti-apo B-100 (JI-H). Remnant lipoprotein particles, as well as betaVLDL, significantly stimulated the proliferation of porcine coronary artery smooth muscle cells in a concentration-dependent manner, whereas very low density lipoprotein (d < 1.006) was virtually ineffective. These observations are consistent with recent reports that triglyceride-rich lipoprotein remnants, which are rich in apo E as well, are atherogenic.

Platelet activation may have a pathophysiological role in Raynaud's phenomenon (RP). However, previous studies have shown conflicting results. This may be related to patient selection and the choice of platelet function assay. In this study, we have assessed platelet function of 30 patients with severe RP with (n = 14) or without (n = 16) systemic sclerosis (SSc), using a whole blood platelet aggregation (PA) assay. Raynaud's medication or other drugs which may affect PA were stopped at least 2 weeks previously. Spontaneous whole blood PA and that induced by 0.5 microM adenosine diphosphate and 0.6 and 1 microgram/ml collagen were significantly increased in both groups of patients when compared with controls. There were no significant differences in PA between the 2 groups of patients. Using a more physiological assay, patients with severe RP, whether or not associated with SSc, were shown to have abnormally increased platelet activity. Hyperactive platelets may further impede blood flow in RP.