Hypoxia-inducible factor 1␣ (HIF-1␣) functions as a transcription factor that is activated by decreased cellular oxygen concentrations to induce expression of a network of genes involved in angiogenesis, erythropoiesis, and glucose homeostasis. Here we demonstrate that two members of the SRC-1/p160 family of transcriptional coactivators harboring histone acetyltransferase activity, SRC-1 and transcription intermediary factor 2 (TIF2), are able to interact with HIF-1␣ and enhance its transactivation potential in a hypoxiadependent manner. HIF-1␣ contains within its C terminus two transactivation domains. The hypoxia-inducible activity of both these domains was enhanced by either SRC-1 or the CREB-binding protein (

We evaluated the effect of periodical treatment with LDL-apheresis by adsorption to dextran sulfate (Liposorber LA-15) on several aspects related to LDL and Lipoprotein(a) metabolisms, in three homozygous familial hypercholesterolaemic patients with LDL receptor deficiency. The dextran sulfate columns retained apolipoprotein B-containing particles with high affinity and capacity, in such a way that the treatment of a volume of plasma equivalent to three times the patient plasma volume resulted in an 85% decrease of circulating LDL-cholesterol and Lipoprotein(a). The continuous treatment with LDL-apheresis was highly beneficial for these patients since an average plasma concentration lower than 200 mg dl-1 for LDL-cholesterol, and lower than 25 mg dl-1 for Lipoprotein(a) could be achieved by treating the patients once a week. After each apheresis treatment, plasma concentrations of these metabolites progressively returned to the pretreatment, steady-state, levels. The analysis of the rates of return allowed us to estimate the fractional catabolic rates. FCRs of LDL-cholesterol were 0.052, 0.049 and 0.047 pools day-1, and those of apolipoprotein B, 0.065, 0.045 and 0.050 pools day-1 in the three subjects, respectively. These values are much lower than those in normolipidaemic individuals as observed by others, and are in accordance with the LDL-receptor deficiency condition of our patients. Two of them had highly elevated Lipoprotein(a) plasma concentrations, and their FCRs of Lipoprotein(a) were calculated to be 0.112 and 0.066 pools day-1.(ABSTRACT TRUNCATED AT 250 WORDS)

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