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Arterioscler Thromb Vasc Biol ; 39(5): 915-924, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30894011


Objective- Aim of this study was to evaluate changes in LCAT (lecithin:cholesterol acyltransferase) concentration and activity in patients with an acute coronary syndrome, to investigate if these changes are related to the compromised capacity of HDL (high-density lipoprotein) to promote endothelial nitric oxide (NO) production, and to assess if rhLCAT (recombinant human LCAT) can rescue the defective vasoprotective HDL function. Approach and Results- Thirty ST-segment-elevation myocardial infarction (STEMI) patients were enrolled, and plasma was collected at hospital admission, 48 and 72 hours thereafter, at hospital discharge, and at 30-day follow-up. Plasma LCAT concentration and activity were measured and related to the capacity of HDL to promote NO production in cultured endothelial cells. In vitro studies were performed in which STEMI patients' plasma was added with rhLCAT and HDL vasoprotective activity assessed by measuring NO production in endothelial cells. The plasma concentration of the LCAT enzyme significantly decreases during STEMI with a parallel significant reduction in LCAT activity. HDL isolated from STEMI patients progressively lose the capacity to promote NO production by endothelial cells, and the reduction is related to decreased LCAT concentration. In vitro incubation of STEMI patients' plasma with rhLCAT restores HDL ability to promote endothelial NO production, possibly related to significant modification in HDL phospholipid classes. Conclusions- Impairment of cholesterol esterification may be a major factor in the HDL dysfunction observed during acute coronary syndrome. rhLCAT is able to restore HDL-mediated NO production in vitro, suggesting LCAT as potential therapeutic target for restoring HDL functionality in acute coronary syndrome.

Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/fisiopatologia , Lipoproteínas HDL/sangue , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/enzimologia , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Óxido Nítrico/metabolismo , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Sensibilidade e Especificidade , Esterol O-Aciltransferase/sangue
Sci Rep ; 9(1): 20354, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31889114


In the last years increasing attention has been given to the connection between genotype/phenotype and cardiovascular events in subjects with familial hypercholesterolemia (FH). MicroRNAs (miRs) bound to high-density lipoprotein (HDL) may contribute to better discriminate the cardiovascular risk of FH subjects. Our aim was to evaluate the HDL-miR panel in heterozygous FH (HeFH) patients with an LDLR null or defective mutation and its association with pulse wave velocity (PWV). We evaluated lipid panel, HDL-miR panel and PWV in 32 LDLR null mutation (LDLR-null group) and 35 LDLR defective variant (LDLR-defective group) HeFH patients. HDL-miR-486 and HDL-miR-92a levels were more expressed in the LDLR-null group than the LDLR-defective group. When we further stratified the study population into three groups according to both the LDLR genotype and history of ASCVD (LDLR-null/not-ASCVD, LDLR-defective/not-ASCVD and LDLR/ASCVD groups), both the LDLR/ASCVD and the LDLR-null/not-ASCVD groups had a higher expression of HDL-miR-486 and HDL-miR-92a than the LDLR-defective/not-ASCVD group. Finally, HDL-miR-486 and HDL-miR-92a were independently associated with PWV. In conclusion, the LDLR-null group exhibited HDL-miR-486 and HDL-miR-92a levels more expressed than the LDLR-defective group. Further studies are needed to evaluate these HDL-miRs as predictive biomarkers of cardiovascular events in FH.

Nutrients ; 10(10)2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30326655


The development of nutraceutical ingredients has risen as a nutritional solution for health prevention. This study evaluated the effects of Oleactiv®, an ingredient developed for the prevention of atherogenesis, in hypercholesterolemic hamsters. Oleactiv® is a polyphenol-rich ingredient obtained from artichoke, olive and grape extracts as part of fruit and vegetables commonly consumed within the Mediterranean diet. A total of 21 Golden Syrian hamsters were divided into three groups. The standard group (STD) was fed a normolipidemic diet for 12 weeks, while the control group (CTRL) and Oleactiv® goup (OLE) were fed a high-fat diet. After sacrifice, the aortic fatty streak area (AFSA), plasmatic total cholesterol (TC), high-density lipoproteins (HDL-C), non-HDL-C and triglycerides (TG), were assessed. The cholesterol efflux capacity (CEC) of hamster plasma was quantified using a radiolabeled technique in murine macrophages J774. OLE administration induced a significant reduction of AFSA (-69%, p < 0.0001). Hamsters of the OLE group showed a significant decrease of both non-HDL-C (-173 mmol/L, p < 0.05) and TG (-154 mmol/L, p < 0.05). Interestingly, OLE induced a significant increase of total CEC (+17,33%, p < 0,05). Oleactiv® supplementation prevented atheroma development and had positive effects on the lipid profile of hypercholesterolemic hamsters. The increased CEC underlines the anti-atherosclerotic mechanism at the root of the atheroma reduction observed.

Anticolesterolemiantes/farmacologia , Aorta Torácica/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Colesterol/sangue , Suplementos Nutricionais , Hipercolesterolemia/tratamento farmacológico , Polifenóis/farmacologia , Animais , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Doenças da Aorta/sangue , Doenças da Aorta/etiologia , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Linhagem Celular , HDL-Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Mesocricetus , Camundongos , Placa Aterosclerótica , Triglicerídeos/sangue