Turner's syndrome is characterized, amongst other things, by growth retardation with high serum levels of insulin-like growth factor 1 (IGF-I) in relation to growth, by a tendency to autoimmune disease and by insulin resistance with hyperlipidaemia. Assuming a role for IGF-I subresponsiveness in the last two features, the present study was designed to evaluate in patients with Turner's syndrome their monocyte/macrophage response to growth hormone (GH) and to IGF-I with respect to low-density lipoprotein (LDL) degradation and to the monocyte-dependent lymphocyte proliferation. Nineteen patients with Turner's syndrome and puberty-matched control subjects were studied. Monocytes were isolated from the blood of the patients and the control group, and cultured to develop into macrophages. The cells were then incubated with 125I-labelled LDL (25 micrograms of protein mL-1) in the absence or presence of 50 ng mL-1 IGF-I or GH, and cellular lipoprotein degradation was determined. GH and IGF-I effects on T-cell proliferation were measured in autologous mixed lymphocyte reaction Monocytes/macrophages degradation of LDL was lower in Turner's syndrome patients than in control subjects (P < 0.05). IGF-I stimulated LDL degradation by 42 +/- 8% in the control subjects and by only 16 +/- 7% in Turner's syndrome patients (P < 0.05). Control lymphocyte proliferation in AMLR was significantly augmented by 50-100 ng mL-1 GH or IGF-I. Lymphocytes derived from peripheral blood of Turner's syndrome patients remained almost unaffected by either GH or IGF-I. Measurement of IL-2 secretion by purified blastoid T lymphocytes-I. revealed a significant augmentation by 100 ng mL-1 GH and by 50-100 ng mL-1 IGF-I in control subjects, and almost no response in Turner's0 ng syndrome. Turner's syndrome is associated with decreased sensitivity of peripheral blood mononuclear cells to GH and to IGF-I, as is evident by the reduction in LDL degradation, monocyte-stimulated T-lymphocyte proliferation and IL-2 secretion by blastoid T cells.

The influence of 2 different fatty meals, rich in either saturated or polyunsaturated fatty acids, on platelet aggregation in 7 normolipemic subjects and in 10 patiens with phenotype IV hyperlipemia, was studied. 3 h after ingestion of a saturated- or polyunsaturated-fat-rich meal, plasma triglycerides were similarly increased in both groups. 5 h after ingestion of fat of either origin, the plasma triglyceride level in normal subjects returned almost to the fasting level, whereas in patients with hypertriglyceridemia it was still elevated. Platelet aggregation induced by ADP in platelet-rich plasma significantly increased in the normal group 3 h after both meals, whereas in the patient group it increased only after the saturated-fat-rich meal. These results were not changed 5 h after the meals. Postprandial elevated platelet activity was not correlated with increased plasma triglyceride concentration. No changes were found in washed-platelet aggregation in normal subjects, whereas the patient-derived washed platelets showed increased aggregation after the saturated-fat-rich meal. Plasma chylomicrons prepared from both groups during alimentary hyperlipemia inhibited ADP-induced platelet aggregation as well as thrombin-induced platelet ¹⁴C-serotonin release. This study indicates that the intake of fatty meals induces acute disturbance in platelet aggregation, favoring thrombosis. These changes are more comprehensive in hyperlipemic patients and after a saturated-fat-rich meal.

Intracellular cholesterol metabolism is regulated by membrane receptors which selectively bind plasma low density lipoproteins (LDL), the major extracellular source of cholesterol. Human platelets, unlike other cells, are unable to synthesize cholesterol, but bind LDL with specificity. We have shown that very low density lipoproteins (VLDL) and LDL, both of which contain apolipoprotein B compete with 125I-LDL for the platelet binding sites, while high density lipoproteins (HDL) is only able to compete to a limit extent and this by virtue of its apolipoprotein E content. Platelet uptake of both LDL and HDL is saturable at physiologic concentrations of these lipoproteins. The lipoproteins are internalized by the platelet but degradation occurs only to a limited extent. Incubation of LDL AND HDL with gel-filtered platelet results in significant changes in the platelet cholesterol content. IDL ( 1 mg protein/ml) increases cholesterol content by 15% whereas the same concentration of HDL causes a 5% reduction. In the presence of thrombin LDL enhances platelet aggregation by 300% whereas HDL decreases aggregation by 50%.We have thus shown that the lipoprotein platelet interaction alfects both platelet cholesterol content and also platelet aggregation. LDL and HDL have opposing effects and this again highlights their different roles in the atherogenic process.

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