Lecithin—Cholesterol Acyltransferase and the Lipoprotein Abnormalities of Obstructive Jaundice

Agorastos, J.; Fox, C. Iris; Harry, David; McIntyre, Neil

doi:10.1042/cs0540369

Cited by 24 publications

(41 citation statements)

References 23 publications

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“…In the general population, cholesterol-lowering strategies are based mainly on monitoring of LDL cholesterol levels [15]. In the presence of chronic cholestasis, LDL metabolism is highly deranged [7,8], even when hypercholesterolemia of different origin coexists. Therefore, we suggest that monitoring cholesterol-lowering treatment be based on total cholesterol concentrations, with a goal of serum cholesterol levels lower than 240 mg/dL.…”

Section: Opinion Statementmentioning

confidence: 99%

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Hyperlipidemia in chronic cholestatic liver disease

Longo

Crosignani

Podda

2001

Curr Treat Options Gastro

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Hyperlipidemia with a marked increase of low-density lipoprotein (LDL) and high- density lipoprotein (HDL) cholesterol levels is a common feature in patients with chronic cholestatic liver disease. Excess morbidity and mortality from cardiovascular disease has not been reported in these patients. This may be due to the particular lipoprotein pattern observed during chronic cholestasis, characterized by elevated serum HDL cholesterol, which may have a cardioprotective effect. However, in a subgroup of patients with chronic cholestasis, hyperlipidemia is characterized by markedly elevated LDL levels with normal or low HDL levels, probably reflecting hypercholesterolemia with coexisting familial and nutritional origins. Ursodeoxycholic acid, the only drug approved for the treatment of chronic cholestatic liver diseases, has been shown to slightly decrease serum cholesterol concentrations. However, the extent of LDL reduction by ursodeoxycholic acid may be insufficient to protect this subgroup of patients from increased cardiovascular risk. Patients in this subgroup probably would benefit from dietary modification, weight loss, and the administration of specific lipid-lowering drugs. Cholestyramine, which is the first-line treatment for pruritus in chronic cholestasis, may be also indicated for its cholesterol-lowering capacity in patients with hypercholesterolemia who complain of pruritus. Administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (simvastatin or pravastatin, 20 mg/d) should be limited to hypercholesterolemic patients with mild chronic cholestatic liver diseases in whom HDL serum levels are below the protective range or if additional risk factors for cardiovascular diseases are present.

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Section: Opinion Statementmentioning

confidence: 99%

“…lating high-density lipoprotein (HDL) cholesterol [7][8][9], which may have a cardioprotective effect. However, it should be highlighted that these observations may be distorted by the fact that these patients are affected by a chronic, ultimately fatal, liver disease [10].…”

Section: Opinion Statementmentioning

confidence: 99%

Hyperlipidemia in chronic cholestatic liver disease

Longo

Crosignani

Podda

2001

Curr Treat Options Gastro

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“…Normal erythrocytes were incubated for I min at 370C with HDL from jaundiced patients at a concentration similar to that in plasma (500 ,ug/ml) (19,20); echinocytes I, II, or III appeared in the suspension (Table I, Fig. 4).…”

Section: And E)mentioning

confidence: 99%

Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins.

Owen¹,

Brown²,

Harry³

et al. 1985

J. Clin. Invest.

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Echinocytes were frequently found in patients with liver disease when their blood was examined in wet films, but rarely detected in dried, stained smears. When normal erythrocytes (discocytes)were incubated with physiologic concentrations of the abnormal high density lipoproteins (HDL) from some jaundiced patients, echinocytosis developed within seconds. Other plasma fractions were not echinocytogenic. There was a close correlation between the number of echinocytes found in vivo and the ability of the corresponding HDL to induce discocyte-echinocyte transformation. On incubation with normal HDL, echinocytes generated in vitro rapidly reverted to a normal shape, and echinocytes from patients showed a similar trend. Echinocytosis occurred without change in membrane cholesterol content, as did its reversal, and was not caused by membrane uptake of lysolecithin or bile acids. Abnormal, echinocytogenic HDL showed saturable binding to -5,000 sites per normal erythrocyte with an association constant of 108 M-'. Nonechinocytogenic patient HDL and normal HDL showed only nonsaturable binding. Several minor components of electrophoretically separated erythrocyte membrane proteins bound the abnormal HDL; pretreatment of the cells with trypsin or pronase reduced or eliminated binding. Echinocytosis by abnormal HDL required receptor occupancy, rather than transfer of constituents to or from the membrane, because cells reversibly prefixed in the discoid shape by wheat germ agglutinin, and then exposed to abnormal HDL, did not become echinocytes when the HDL and lectin were successively removed. Binding did not cause dephosphorylation of spectrin. We conclude that the echinocytes of liver disease are generated from discocytes by abnormal HDL, and we infer that the shape change is mediated by cell-surface receptors for abnormal HDL molecules.

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“…It has been shown that bile acid regurgitation resulting from bile duct damage, together with a decrease in LCAT activity due to liver cell damage, is the main contributor to the formation of LpX [5,[7][8][9][10]33,34,37,38]. Furthermore, Elferink and colleagues [39] demonstrated that Mdr2 (Abcb4) knockout mice failed to form LpX even during cholestasis; they suggested that the expression of MDR3 regulated the formation of LpX.…”

Section: Discussionmentioning

confidence: 96%

“…However, our previous work provided evidence that PFIC patients have dyslipidemia, characterized by the accumulation of triglyceride (TG)-rich low-density lipoprotein (LDL) and depleted high-density lipoprotein (HDL), and a predisposition to cardiovascular disorders involving atherosclerosis [4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%