Subject(s)
Concept Formation , Venous Insufficiency , Chronic Disease , Humans , Venous Insufficiency/therapy , Venous PressureABSTRACT
BACKGROUND: ATP-binding cassette A1 (ABCA1) and G1 (ABCG1) mediate cholesterol efflux from lipid-laden macrophages, thus promoting anti-atherosclerotic outcomes. The mechanism(s) linking treatment with statins and ABCA1/ABCG1 in human atherosclerosis are not fully understood and require further investigation. Therefore, we studied whether short-term treatment with low- or high-dose rosuvastatin may affect ABCA1 and ABCG1 expression in human atherosclerotic plaques. METHODS: Seventy patients with severe stenosis of the internal carotid artery were randomized to receive low (10â¯mg/day) or high (40â¯mg/day) dose rosuvastatin for 12â¯weeks before elective endarterectomy. As controls, we analyzed a reference group of 10 plaques from subjects with hypercholesterolemia but not receiving statin treatment and an additional set of 11 plaques collected from normocholesterolemic patients. On atherosclerotic plaques, ABCA1 and ABCG1 expression was evaluated at RNA level by qPCR and at protein level by immunoblotting and immunohistochemistry. RESULTS: Both rosuvastatin doses were associated with lower plaque ABCA1 mRNA levels and with a trend toward reduction for ABCG1. However, ABCA1 protein was paradoxically higher in patients treated with high-dose rosuvastatin and was associated with lower levels of miR-33b-5p, a microRNA known as a regulator of ABCA1. Multivariate analyses showed that the effect is cholesterol-independent. Finally, no effects were found for ABCG1 protein. CONCLUSIONS: High-dose rosuvastatin increases macrophage ABCA1 protein levels in human atherosclerotic plaque despite mRNA reduction in a mechanism unrelated to plasma cholesterol reduction and potentially involving miR-33b-5p. This pathway may reflect an additional feature contributing to the anti-atherosclerotic effect for high-dose rosuvastatin. TRIAL REGISTRATION: ISRCTN16590640.
Subject(s)
ATP Binding Cassette Transporter 1/blood , Cholesterol/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Plaque, Atherosclerotic/blood , Plaque, Atherosclerotic/drug therapy , Rosuvastatin Calcium/administration & dosage , ATP Binding Cassette Transporter 1/biosynthesis , Aged , Aged, 80 and over , Anticholesteremic Agents/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , MaleABSTRACT
Sexual abuse, even when it occurs during childhood, may manifest symptoms only in adolescence by the effect of the resignifcation of infantile sexuality, characteristic of that vital moment. In cases of child sexual abuse, in the face of the disruption of impulses and identifcations that occurs in adolescence, there can be trauma that limits the possibilities of processing the psychic apparatus, even in the course of a psychotherapeutic treatment. The acting out reveals itself in transference, it calls for the analyst to relocate the suffering of his patient.
