RESUMO
Congenital coronary artery fistula (CAF) is an infrequent vascular anomaly that establishes a direct link between an epicardial coronary artery and a cardiac chamber, major vessels, or other vascular structures. In this case there was an aneurysmal-CAF between a left main trunk and the right atrium, which was initially diagnosed as a Kawasaki disease by transthoracic echocardiography and subsequently confirmed by coronary angiography and multi-slice CT angiography. A multi-slice CT angiography might well become the modality of choice for the characterization of these rare congenital anomalies.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Aneurisma Coronário/complicações , Aneurisma Coronário/diagnóstico por imagem , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico por imagem , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Fístula Vascular/complicações , Fístula Vascular/diagnóstico por imagem , Adulto , Feminino , Humanos , RadiografiaRESUMO
BACKGROUND: Platelet-activating factor acetylhydrolyse (PAF-AH) is an enzyme that degrades PAF and bioactive oxidized lipids. However, it has been reported to be a risk factor for coronary heart disease. The present study examined the effects of cholesterol feeding and simvastatin treatment on plasma PAF-AH activity. METHODS: Japanese White rabbits (n=22) were fed a diet containing 0.3% cholesterol and 3% corn oil for 1 month, and then divided into two groups that continued to receive this diet with (treated) or without (control) treatment with simvastatin (0.01%) for another 2 months. RESULTS: Cholesterol feeding increased and simvastatin treatment decreased apolipoprotein (apo) B-containing lipoprotein subfractions as characterized by capillary isotachophoresis, serum levels of total cholesterol, phospholipids, LDL-C, apoE, plasma and LDL-associated PAF-AH (LDL-PAF-AH) activities, and plasma lyso-PC concentration. Cholesterol feeding also increased apoB levels but decreased the LDL-PAF-AH/LDL-C ratio and did not change the plasma PAF-AH/lyso-PC ratio. Simvastatin treatment did not affect apoB levels and only slightly increased the LDL-PAF-AH/LDL-C ratio. Secretion of PAF-AH activity from monocyte-derived macrophages was increased by cholesterol feeding but not affected by simvastatin treatment. These results indicate that PAF-AH activity is increased by cholesterol feeding due to increased secretion of PAF-AH activity from macrophages and that PAF-AH activity is decreased by simvastatin due to increased removal of lipid and enzyme contents of LDL particles. CONCLUSION: Cholesterol elevation by cholesterol feeding and cholesterol-lowering by simvastatin modulate plasma PAF-AH activity by different mechanisms.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Colesterol na Dieta/administração & dosagem , Hipolipemiantes/administração & dosagem , Lisofosfatidilcolinas/sangue , Sinvastatina/administração & dosagem , Animais , Colesterol na Dieta/farmacologia , Eletroforese Capilar , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Hipolipemiantes/farmacologia , Lipoproteínas LDL/sangue , Masculino , Coelhos , Sinvastatina/farmacologiaRESUMO
BACKGROUND: Inhibition of cholesteryl ester transfer protein (CETP) is an efficient way to increase high-density lipoprotein (HDL) levels in humans. We investigated the effects of the inhibition of CETP activity by a CETP inhibitor, JTT-705, on the function and composition of HDL particles. METHODS AND RESULTS: Japanese white rabbits were fed either normal rabbit chow LRC-4 (n=10) or a food admixture of LRC-4 and 0.75% JTT-705 (n=10) for 7 months. JTT-705 significantly inhibited CETP activities, increased HDL cholesterol (HDL-C) levels and the ratio of HDL2-C/HDL3-C, and decreased the fractional esterification rate of cholesterol in HDL, indicating preferentially increased large HDL particles. Treatment with JTT-705 increased all of the 3 charge-based HDL subfractions as determined by capillary isotachophoresis: fast-migrating, intermediate-migrating, and slow-migrating HDL. The percentage of slow HDL, ie, apolipoprotein E (apoE)-containing HDL and levels of apoE in HDL fraction, was also increased. JTT-705 treatment increased serum paraoxonase activity and HDL-associated platelet-activating factor acetylhydrolase activity, but decreased the plasma lysophosphatidylcholine concentration. CONCLUSIONS: Inhibition of CETP activity by JTT-705 not only increased the quantity of HDL, including HDL-C levels and charge-based HDL subfractions, but also favorably affected the size distribution of HDL subpopulations and the apolipoprotein and enzyme composition of HDL in rabbits.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Apolipoproteínas E/química , Apolipoproteínas E/metabolismo , Arildialquilfosfatase/metabolismo , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/fisiologia , Glicoproteínas/antagonistas & inibidores , Glicoproteínas/fisiologia , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Compostos de Sulfidrila/farmacologia , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Amidas , Animais , Apolipoproteínas E/sangue , Arildialquilfosfatase/sangue , Proteínas de Transferência de Ésteres de Colesterol , HDL-Colesterol/sangue , Eletroforese Capilar/métodos , Ésteres , Lipoproteínas HDL/sangue , Lisofosfatidilcolinas/sangue , CoelhosRESUMO
BACKGROUND: Inhibition of cholesteryl ester transfer protein (CETP) is an effective way to increase HDL levels in animals and humans. The effects of a CETP inhibitor, JTT-705, on the in vivo kinetics of apolipoprotein (apo) A-I and apo A-I gene expression in the liver and intestine were investigated. METHODS: Japanese White rabbits were randomly fed normal rabbit chow LRC-4 (n=10, control) or a food admixture of LRC-4 and 0.75% JTT-705 (n=10, treated) for 7 months. An in vivo kinetics study of apo A-I was performed by injecting rabbit 125I-apo A-I, and apo A-I mRNA levels were quantified by RT-PCR. RESULTS: JTT-705 significantly inhibited CETP activities, increased serum levels of HDL-cholesterol (C), HDL2-C, HDL-phospholipid, and apo A-I, and decreased HDL-triglyceride levels. The synthetic rate of apo A-I was higher in the treated rabbits than in control rabbits (13.7 +/- 2.6 versus 9.5 +/- 1.3 mg/kg per day, P < 0.05), while the fractional catabolic rate was similar in the two groups. JTT-705 increased apo A-I mRNA levels in the liver without affecting those in the intestine. CONCLUSION: Inhibition of CETP activity by JTT-705 increases HDL levels by increasing the synthesis of apo A-I, suggesting that it could be a promising therapeutic approach for atherosclerosis.
Assuntos
Apolipoproteína A-I/biossíntese , Apolipoproteína A-I/sangue , Proteínas de Transporte/antagonistas & inibidores , Glicoproteínas , Amidas , Animais , Apolipoproteína A-I/genética , Proteínas de Transferência de Ésteres de Colesterol , HDL-Colesterol/sangue , Ésteres , Expressão Gênica , Lipoproteínas HDL/sangue , Lipoproteínas HDL2 , Masculino , Coelhos , Compostos de Sulfidrila/farmacologia , Triglicerídeos/sangueRESUMO
The kinetics of in vivo clearance of apolipoprotein (apo) A-I radioiodinated by the iodine monochloride (ICI) method of McFarlane [McFarlane, A.S. (1958) Efficient Trace-Labelling of Proteins with Iodine, Nature 182, 53] as modified by Bilheimer and co-workers [Bilheimer, D.W., Eisenberg, S., and Levy, R.I. (1972) The Metabolism of Very Low Density Lipoprotein Proteins. I. Preliminary in vitro and in vivo Observations, Biochim. Biophys. Acta 260, 212-221] and by using the IODO Beads Iodination Reagent were evaluated in rabbits. Both human apoA-I and rabbit HDL radioiodinated by the IODO Beads Iodination Reagent were cleared faster from plasma of rabbits than those radiolabeled by the ICI method. However, the different radiolabeling procedures in the ICI method, i.e., apoA-I radiolabeled either exogenously or in situ as a part of intact HDL, were not associated with a significant difference in the in vivo kinetics of apoA-I in rabbits if apoA-I was prepared by the guanidine HCI method and used fresh. 125I-ApoA-I subjected to delipidation and lyophilization was cleared only slightly faster from the plasma of rabbits than fresh 125I-apoA-I. We also found that apoA-I separated by the guanidine HCI method and used fresh was cleared faster from the plasma of rabbits when it was injected as free apoA-I without adding serum albumin or after in vitro incubation with rabbit HDL than when injected after reassociation with rabbit plasma. We conclude that the ICI method is a more appropriate radioiodination method for studying the in vivo kinetics of HDL than the IODO Beads Iodination Reagent and that the in vitro incubation conditions before injection are important factors that affect the in vivo kinetics of apo A-I.