Browsing by Author "Perales, José"

Se ha analizado el perfil de llpoprotelnas y apollpoprotelnas en un grupo de pacientes con hepatopatia cr6nica, tratando de valorar posibles diferencias en cuanto al grado de deterioro funcional del mismo y a la presencia de colestasis. Mtrooos: Se han estucliado 21 sujetos con clrrosis hepatica y 12 con clrrosis biliar primaria. Se divldieron en dos subgrupos cada uno, atendiendo a la exlstencia de descompensaci6n cilnica y el estadio de Scheuer, respectivamente. La separacl6n de lipoprotelnas se efectu6 medlante ultracentrifugaci6n del plasma, estudiandose los lipldos y de su composlci6n en apolipoprotelnas. La lipoproteina X se ldentlflc6 rnediante electroforesls en gel de agarosa. Rtsumoos: En los grupos de menor afectacl6n solo se reglstraron camblos mlnlmos: disminucl6n del colesterol esteriflcado y de Apo E en '(LDL en los clrr6tlcos y un aumento de colesterol-HDL en la cirrosis billar. En los cirr6tlcos descompensados estaban dismlnuidos VLDL, HDL, trigliceridos y colesterol esteriflcado. Las fracclones de Apo C en VLDL eran normales y los niveles de Apo E indetectables. En los pacientes con clrrosls blliar avanzada, . estaban elevados los trigllceridos, el colesterol llbre y las LDL, y dismlnuldos el colesterol esteriflcado y las HDL; las VLDL estaban enriquecldas en Apo C-110. La lipoprotelna X se detect6 en todos estos sujetos y en la mltad de los drr6ticos descompensados. , CoNCLUSIONts: La hepatopatia cr6nlca avanzada se asoda con un descenso de los nlveles de las llpoproteinas de origen hepatico y la ausencla de Apo E en VLDL, probablemente debldo a un falio en su sintesls. El perfll de los pacientes con drrosls blliar primaria avanzada deflnlrla la colestasis cr6nica y se caracterlza por la presencia de llpoprotelna X. la elevad6n del colesterol ilbre y el descenso del colesterol-HDL; las VLDL, que estan aumentadas, son ricas en Apo C-11. Los datos muestran la dlstinta repercusi6n de estas patologias en la composici6n de apoprotelnas de las VLDL

Liver disease is accompanied by major qualitative and quantitative disturbances in plasma lipoprotein metabolism, the extent and intensity of which depend on the degree of parenchymal damage, cholestasis, or both. The main objective of this study was to determine the cholesteryl ester transfer CETP activity and its association with the lipoprotein neutral lipid composition in patients with either liver cirrhosis or cholestasis, as compared to normal controls. Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins were measured by conventional methods, and the fatty acid composition was established by gas chromotography; CETP activity in lipoprotein-deficient plasma was measured by determining the transfer of [3H]cholesteryl esters from HDL to VLDL. Lipoprotein lipase and hepatic lipase activities were measured in post-heparin plasma by radiochemical methods. In patients with liver cirrhosis, low levels of VLDL, HDL, apo B, and Lp(a) were observed, as well as a change in the composition of HDL particles, with increases in the relative proportion of triglyceride and free cholesterol. Respectively, the last two changes could be attributed in part to the low hepatic lipase activity observed in this study, and to the low lecithin:cholesterol acyltransferase activity previously observed by others. In patients with cholestasis, a moderate hyperlipidemia due to the elevation of LDL was found. In contrast, HDL and apo A-I levels were very low reflecting a low number of HDL particles, which also had altered compositions with increases in the triglyceride and free cholesterol contents relative to apo A-I and esterified cholesterol, respectively. As regards the fatty acid composition of lipoprotein lipids, the two groups of patients showed, in general, a lower proportion of linoleic acid and a compensating higher proportion of oleic acid as compared to the controls, changes that were observed in both cholesteryl esters and triglycerides. In contrast, the proportions of oleic and palmitoleic acids in phospholipids were increased, whereas that of stearic acid was decreased in patients as compared to controls. In patients with liver cirrhosis, as well as in controls, no changes were observed in the fatty acid compositions of cholesteryl ester, triglycerides, or phospholipids among the different lipoproteins, which probably reflects the equilibration reached by the action of CETP. In patients with cholestasis, no differences were observed in fatty acid composition among the lipoprotein phospholipids but, interestingly, cholesteryl esters from VLDL had a significantly lower linoleic acid content than those from HDL, whereas triglycerides from VLDL had significantly higher oleic acid and lower linoleic acid contents than those from HDL. This distinct fatty acid composition of the neutral lipids between lipoproteins was associated with a significant decrease (25%) in the cholesteryl ester transfer activity in patients with cholestasis. We suggest that fat malabsorption due to the biliary defect may induce a decrease in cholesteryl ester transfer protein synthesis or secretion, which in turn would slow the equilibration of the neutral lipids among plasma lipoproteins.

Liver damage and alterations in the exocrine function of the gland lead to a profound alteration of the :,rna lipoprotein profile. To determine whether hepatic disease results in changes in the lipoprotein fatty acid ·,,cnposition, i.e. to determine whether liver function influences the homeostasis of complex lipids in plasma, we ~,i.ltcd the fatty acid profile of lipids from VLDL, LDL and HDL, as well as from total plasma, in thirty-one .,.m:nts of both sexes with hepatobiliary pathology ( compensated liver cirrhosis, uncompensated liver cirrhosis, -t:rnary biliary cirrhosis, other intrahepatic cholestasis, and acute viral hepatitis). We also studied a group of healthy ,.lulls as controls. We present the lipoprotein profile and the fatty acid composition (myristic Cl4, palmitic Cl6, ,,ilrnitoleic Cl6: l, stearic C18, oleic C18: 1, linoleic Cl8: 2, eicosatrienoic C20: 3co6 and arachidonic C20: 4) ,i ltpoprotein and total plasma triacylglycerols, cholesteryl esters and phospholipids. The main observation of this .n,Jy is that, despite the profound changes in the lipoprotein profile and the lower abundance of polyunsaturated t,nr acids in complex lipids, the composition of all triagylglycerols, cholesteryl esters and phospholipids is .~- similar for the corresponding lipoproteins of patients with hepatobiliary disease and of control subjects. nu~ indicates that in the controls as in the studied patients, the exchange of lipids between plasmatic 3P'Proteins is very rapid and demonstrates the possible importance of the extrahepatic synthesis of cholesteryl e11er transfer protein.