Cholesterol Esterase Synthesis Research Articles

Complex of tris(2-hydroxyethyl)amine and zinc bis(2-methylphenoxyacetate) as inhibitor of acid cholesterol esterase synthesis in blood platelets and mononuclear cells

Application of tris(2-hydroxyethyl)amine and zinc bis(2-methylphenoxyacetate) complex (zincatrane) in experimental atherosclerosis in rabbits leads to decrease in the levels of cholesterol and total lipids in blood platelets (Tc) and monocytes (Mc). The results of enzymatic analysis show that atherogenesis is accompanied by increased activity of acid cholesterol esterase by 66% in Mc and by 55% in Tc compared to standard values. Intramuscular administration of zincatrane at a dose of 10 mg kg−1 decreases the activity of acid cholesterol esterase by almost 35% in Mc and by 26% in Tc compared to the control group. It has been also revealed that zincatrane possesses heparin-like effect, which is expressed in increased thrombin clotting time, blood clotting time and plasma recalcification time as well as in the decreased thrombocyte aggregation. It is assumed that zincatrane stimulates production of endogenous heparin.

Synthesis of cholesterol esterase by monocyte-derived macrophages: a potential role in the biodegradation of poly(urethane)s.

Many studies have described the role of monocyte-derived macrophages (MDM) in inflammation leading to atherosclerosis, a process in which alterations in the metabolism of cholesterol esters is well established. On the other hand, the mechanism of MDM activation in response to biomaterial surfaces is still not well understood. Several studies have described the different degrees of activation of monocytes on poly(urethane) surfaces by measuring the release of early markers of differentiation, such as cytokines. It has been possible to decrease MDM activation in contact with materials by modifying the material surface with antioxidants. Therefore, it has been proposed that it is the reactive oxygen species provided by MDM which are responsible for deleterious effects observed in material-derived inflammation. A recent study has shown that one of the markers of the degree of differentiation of MDM is the synthesis of cholesterol esterase (CE), an enzyme demonstrated as causing biodegradation of polyester(urethane)s and more recently polyether- and polycarbonate-poly(urethane)s as well. In this review article, markers used to assess MDM differentiation on material surfaces will be described and related to the activation of MDM. In particular, the CE accumulation in MDM which is associated with atherosclerosis will be related to its degradative potential during chronic inflammation. How this may impact on the biostability of implanted poly(urethane) medical devices is discussed.

Differential synthesis of cholesterol esterase by monocyte-derived macrophages cultured on poly(ether or ester)-based poly(urethane)s.

Monocytes adherent to implanted biomaterials differentiate into macrophages while synthesizing large amounts of degradative enzymes, including cholesterol esterase (CE), which previously has been shown to degrade poly(urethane)s. Human peripheral blood monocytes were cultured on tissue culture grade polystyrene (PS), and two model poly(urethane)s were synthesized from (1) polycaprolactone (PCL) and (2) polytetramethylene oxide (PTMO), both with 2,4-toluene diisocyanate (TDI) and ethylene diamine (ED). The increase in CE and total protein per cell were measured on days 8 and 28 in culture and normalized to the DNA content per cell. At day 8 there consistently were fewer cells remaining on the PTMO-based polymer than on the PCL-based polymer or the PS (p < 0.05). When comparing day 28 to day 8, there was more CE activity and protein per cell on all materials. However, there was a disproportionate synthesis of CE per mg of total protein on PS and TDI/PCL/ED whereas on PTMO there was not. Significantly, there was more protein and CE per cell on PTMO than on PS or TDI/PCL/ED (p < 0.05). This in vitro model system of the chronic phase of inflammation has shown that it is possible to culture monocytes for a month and assess the material surface itself as a potent activator of the differentiation into macrophages without secondary stimulation. Since CE has been shown to degrade poly(ether and ester)-based poly(urethane)s, the differential production of this enzyme relative to the total protein on different surfaces may impact on the potential long-term biostability of an implanted material.

Cholesterol, cholesterol esters and cholesterol esterase in the sciatic nerve during development of the chick.

Abstract— Changes in the contents of cholesterol and cholesterol ester and in the activity of cholesterol esterase (EC 3.1.1.13) in the sciatic nerve of the chick during development were measured. The ratio of cholesterol ester/cholesterol was an inverse function of the activity of the esterase (i.e. when the ratio was high, the activity of the enzyme was low, and vice versa). The synthesis of cholesterol esterase was inhibited after addition of actinomycin D both in ovo and in vitro.

ROLE OF BILE AND PANCREATIC JUICE IN CHOLESTEROL ABSORPTION AND ESTERIFICATION.

Absence of bile and pancreatic juice in the intestinal tract totally abolished absorption of cholesterol-4-C14 into thoracic duct lymph. Similarly, intestinal cholesterol esterase activity approached zero in animals lacking both bile and pancreatic juice. Intestinal cholesterol esterase could still be demonstrated in animals deprived of pancreatic juice, but which received an infusion or intragastric administration of bile salts. Absorption of cholesterol was shown to occur even in the complete absence of pancreatic juice, provided bile salts were present in the intestinal tract. Some synthesis of cholesterol esterase by the intestinal or reactivation of residual cholesterol esterase in the presence of bile salts is postulated. Thus, pancreatic secretion is not absolutely required for cholesterol absorption, although it has a stimulating effect in the presence of bile salts. This effect is attributed to its cholesterol esterase content. In the presence of bile salts, the process of esterification is postulated to be a rate-limiting step during intestinal absorption of dietary cholesterol.