| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Transfer of cholesterol and diacylglycerol from lipophorin to Bombyx mori ovarioles in vitro: role of the lipid transfer particle Jouni, Z. E., N. Takada, et al. (2003), Insect Biochem Mol Biol 33(2): 145-53. Abstract: The objective of this study was to characterize the transfer of diacylglycerol (DAG) and cholesterol from larval Bombyx mori lipophorin to ovarioles. Transfer studies were carried out by incubating pupal ovarioles (5-day) with (3)H-cholesterol and (3)H-DAG-labeled lipophorin under different conditions. Transfer of both cholesterol and DAG exhibited hyperbolic dependency on lipophorin concentration with apparent Km values of 0.83 +/- 0.17 mg/ml and 0.74 +/- 0.16 mg/ml, respectively. Pretreatment of ovarioles with anti-lipid transfer particle (LTP) IgG significantly inhibited transfer of labeled DAG to ovarioles (75%) and not cholesterol. Injection of B. mori pupae (day 4) with anti-LTP IgG significantly affected the weight (65%), number of eggs (49%), amount of lipid (74%), and protein (65%) of the adult ovaries. Matured eggs had a very faint yellow color and deformed shape compared to controls. The inhibitory effect demonstrates the active role LTP plays in growth of ovaries, development, and oogenesis. The effect on vitellogenin shortage on egg development and maturation was determined by implanting ovaries in male recipients that lack vitellogenin. An 80% decline in egg production was observed. However, the mature eggs were normal in shape, color, and lipid content. Thus, restricting lipid or protein delivery to developing ovaries would dramatically affect choriogenesis. |
| Transfer of cholesterol between high density lipoproteins and cultured rat Sertoli cells Fofana, M., J. C. Maboundou, et al. (1996), Biochem Cell Biol 74(5): 681-6. Abstract: In the testes, the Sertoli cells are separated from the blood capillaries by the basement membrane, thereby excluding the passage of low density lipoproteins (LDLs) but allowing the passage of high density lipoproteins (HDLs). The present study examines first the capacity of Sertoli cells to uptake cholesterol from HDL and secondly the role of apolipoproteins (apo) A-I and E in cholesterol flux between HDL and cultured rat Sertoli cells. In the presence of HDL in cultured medium, rat Sertoli cells accumulated few amounts of esterified cholesterol. Incubation of 14C cholesterol-labelled Sertoli cells with 3Hcholesterol-labelled HDL showed that the amount of cholesterol influx slightly exceeded its efflux, thus resulting in a net uptake of cholesterol from HDL to rat Sertoli cells. The amount of HDL-cholesterol converted to steroids by Sertoli cells was about 32% of influx. Uptake of cholesterol by Sertoli cells was three times higher with phospholipid-apo A-I vesicles and seven times higher with phospholipid- apo E vesicles than that with phospholipid vesicles without apolipoprotein. Phospholipid- apo A-I vesicles promoted cholesterol efflux at the same rate as native HDL and twice as efficiently as phospholipid- apo E vesicles. Thus, this study shows that rat Sertoli cells have the capacity to take up HDL-cholesterol for membrane renewal and steroid production mainly by apo E dependent pathways. |
| Transfer of cholesterol between phospholipid vesicles mediated by the steroidogenic acute regulatory protein (StAR) Tuckey, R. C., M. J. Headlam, et al. (2002), J Biol Chem 277(49): 47123-8. Abstract: The steroidogenic acute regulatory protein (StAR) mediates the acute stimulation of steroid synthesis by tropic hormones in steroidogenic cells. StAR interacts with the outer mitochondrial membrane and facilitates the rate-limiting transfer of cholesterol to the inner mitochondrial membrane where cytochrome P-450scc converts this cholesterol into pregnenolone. We tested the ability of N-62 StAR to transfer cholesterol from donor vesicles containing cholesterol but no cytochrome P-450scc to acceptor vesicles containing P-450scc but no cholesterol, using P-450scc activity as a reporter of the cholesterol content of synthetic phospholipid vesicles. N-62 StAR stimulated P-450scc activity in acceptor vesicles 5-10-fold following the addition of donor vesicles. Transfer of cholesterol to acceptor vesicles was rapid and sufficient to maintain a linear rate of pregnenolone synthesis for 10 min. The effect of N-62 StAR in stimulating P-450scc activity was specific for cholesterol transfer and was not due to vesicle fusion or P-450scc exchange between vesicles. Maximum stimulation of P-450scc activity in acceptor vesicles required preincubation of N-62 StAR with phospholipid vesicles prior to adding donor vesicles. The amount of N-62 StAR causing half-maximum stimulation of P-450scc activity in acceptor vesicles was 1.9 microm. Half-maximum stimulation required more than a 10-fold higher concentration of R182L N-62 StAR, a mutant associated with congenital lipoid adrenal hyperplasia. N-62 StAR-mediated transfer of cholesterol between vesicles showed low dependence on the cholesterol concentration in the donor vesicles. Thus StAR can transfer cholesterol between synthetic membranes without other protein components found in mitochondria. |
| Transfer of cholesterol from macrophages to lymphocytes in culture de Bittencourt Junior, P. I. and R. Curi (1998), Biochem Mol Biol Int 44(2): 347-62. Abstract: A major feature of macrophage metabolism is its capacity to produce and export cholesterol. Several reports have shown that the manipulation of lymphocyte cholesterol content elicits important changes in lymphocyte proliferation. These findings lead to an inquiry as to whether macrophage-derived cholesterol released into the lymphocyte surroundings may be transferred to the latter thus affecting lymphocyte function. In this study, cholesterol transfer from macrophages to lymphocytes was examined in vitro using rat cells in culture. The findings indicate that there may be a significant transfer of cholesterol from 4-14Ccholesterol labeled resident peritoneal macrophages to mesenteric lymph node resting lymphocytes (up to 173.9 +/- 2.7 pmol/10(7) lymphocytes/10(7) macrophages when co-cultivated for 48 h), in a lipoprotein-dependent manner. This represents the mass transfer of ca. 17 nmoles of cholesterol molecules per 10(7) lymphocytes from 10(7) macrophages (calculated on the basis of specific radioactivity incorporated into macrophages after the pre-labelling period), which suggests that macrophages are capable of replacing the whole lymphocyte cholesterol pool every 21 h. Moreover, an 111%-increase in the total cholesterol content of lymphocytes was found after co-cultivation with macrophages for 48 h. When compared to peritoneal cells, monocytes/macrophages obtained from circulating blood leukocytes presented a much higher cholesterol transfer capacity to lymphocytes (3.06 +/- 0.10 nmol/10(7) lymphocytes/10(7) macrophages co-cultivated for 24 h). Interestingly, inflammatory macrophages dramatically reduced their cholesterol transfer ability (by up to 91%, as compared to resident macrophages). Cholesterol transfer may involve a humoral influence, since it is not only observed when cells are co-cultivated in a single-well chamber system (cells in direct contact), but also in a two-compartment system (where cells can communicate but not by direct contact). Co-cultivation with macrophages decreased the basal incorporation of 2-14Cthymidine into lymphocyte DNA and the addition of cholesterol to lymphocyte culture media also impaired the lymphocyte proliferative response to the mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS). The above results suggest that macrophages may transfer cholesterol to lymphocytes (from both lymph nodes and blood), thus regulating lymphocyte function by raising the intracellular cholesterol content and suppressing lymphocyte proliferative activity. If this is so, a modulatory role for the transfer of cholesterol in both physiological (e.g. immune response) and pathological conditions (e.g. atherosclerosis) may be postulated. This hypothesis is currently under investigation in our laboratory. |
| Transfer of cholesterol from Ob1771 cells or LDL to reconstituted, defined high density lipoproteins Jonas, A., K. Bottum, et al. (1994), J Lipid Res 35(5): 860-70. Abstract: We used defined, reconstituted high density lipoproteins (rHDL) to study the effects of structure and composition of these particles on their role as cholesterol acceptors from cell membranes or from low density lipoproteins (LDL). Three discoidal rHDL and one spherical rHDL with distinct apolipoprotein A-I conformations, diameters and compositions were used in conjunction with Ob1771 cells to measure the rate of 3Hcholesterol efflux from the cells, direct binding to the cells, and competition with native HDL3 for binding. In addition, the same rHDL particles were used to study the kinetics of cholesterol mass transfer from LDL. The results show that the rates of cholesterol transfer depend on the nature of the donor (t1/2 11-19 min from LDL, and t1/2 5 h from the cells), on the phosphatidylcholine/cholesterol ratio in the acceptors (the closer this ratio is to the equilibrium value, the slower is the rate), and on the diameter of the acceptors (the smallest particles have the lowest t1/2 for cholesterol uptake from LDL, and are the most effective acceptors of 3Hcholesterol from cells after their phospholipid content is taken into account). The cholesterol uptake by the rHDL, both from the cells and from LDL, is determined mostly by the phospholipid pool available in the acceptors. Binding to the cells was equivalent for all the rHDL (Kd = 38-67 micrograms/ml) and comparable to HDL3, suggesting that the differences in apoA-I conformation have no effect on the binding to cells. Finally we observed that exposure of rHDL to cells may lead to remodeling of some of the lipoprotein particles. |
| Transfer of lipoprotein(a) and LDL into aortic intima in normal and in cholesterol-fed rabbits Nielsen, L. B., B. G. Nordestgaard, et al. (1995), Arterioscler Thromb Vasc Biol 15(9): 1492-502. Abstract: To study the relative atherogenic potential of lipoprotein(a) Lp(a), the transfer of Lp(a) and LDL into the arterial wall was compared in normal rabbits, cholesterol-fed rabbits, and normal rabbits in which the plasma concentration of Lp(a) before injection of labeled lipoproteins was increased by an intravenous mass injection of 45 mg Lp(a). Aorta was removed either 60 minutes or 180 minutes after intravenous injection of a mixed preparation of human 125I-Lp(a) and 131I-LDL; intimal clearance was calculated as radioactivity in aortic intima/inner media divided by the average concentration of the appropriate radioactivity in plasma and by the length of the exposure time. The intimal clearance of labeled Lp(a) and LDL in the aortic arch after 60 minutes of exposure was 87 +/- 9 and 47 +/- 7 nL.cm-2.h-1 (n = 9) in normal rabbits and 82 +/- 14 and 62 +/- 10 nL.cm-2.h-1 (n = 10) in cholesterol-fed rabbits; after 180 minutes of exposure, the intimal clearance of labeled Lp(a) and LDL was 62 +/- 14 and 84 +/- 21 nL.cm-2.h-1 (n = 6) and 30 +/- 6 and 47 +/- 12 nL.cm-2.h-1 (n = 4) in cholesterol-fed and Lp(a)-injected rabbits, respectively. Linear regression analysis showed positive associations between intimal clearance of the two lipoproteins in all four groups of rabbits in the aortic arch, the thoracic aorta, and the abdominal aorta. Aortic immunoreactivity of human apolipoprotein(a) was detected in the intima in association with fatty streak lesions, predominantly within the cytoplasm of foam cells. These results suggest that Lp(a) is transferred into the aortic intima by a mechanism similar to that for LDL and that Lp(a) can be taken up by intimal foam cells; however, Lp(a) and LDL may be metabolized differently upon entrance into the arterial wall. |
| Transfer of phospholipids and cholesterol from triglyceride-rich emulsions to HDL in rats treated with alloxan, propylthiouracil or ethanol Roland, I. A. and R. C. Maranhao (1993), Braz J Med Biol Res 26(1): 109-18. Abstract: 1. The transfer of lipids that constitute the surface of lipoprotein particles, phospholipids and unesterified cholesterol, from chylomicrons and VLDL to other lipoproteins, mainly HDL, was examined. 2. Emulsions known to mimic the metabolism of chylomicrons labeled with 3H-phosphatidylcholine, 14C-cholesterol or 3H-triolein were injected through a cannula implanted into the carotid artery of male Wistar rats weighing 280-350 g. Plasma clearance of the radioactively labeled emulsion lipid constituents and transfer of surface lipids from the emulsions to native HDL and LDL were measured in plasma samples collected at 2-min intervals during 10 min. 3. The transfer was measured in rats with alloxan-induced diabetes (single intraperitoneal dose, 140 mg/kg body weight) or with propylthiouracil-induced hypothyroidism (0.1% v/v in drinking water for 30 days), or given ethanol (20% in drinking water) for a period of 30 days, and in control rats. 4. The entry of emulsion phospholipids into the HDL fraction was not affected by the different treatments (controls: 9.3 +/- 0.6% of injected radioactivity, N = 8; diabetes: 12.5 +/- 2.4%, N = 9; hypothyroidism: 10.9 +/- 0.9%, N = 13; ethanol: 7.8 +/- 0.9%, N = 5). However, phospholipid transfer to the LDL fraction was increased in diabetes (10.0 +/- 2.3%) and hypothyroidism (12.1 +/- 1.3%) compared to controls (6.7 +/- 0.9%). Transfer of unesterified cholesterol from the emulsions to LDL and HDL was increased in both diabetic and hypothyroid rats (controls, LDL: 1.6 +/- 0.6%, HDL: 2.5 +/- 0.6, N = 5; diabetes, LDL: 5.3 +/- 1.2, HDL: 8.4 +/- 2.1 N = 5; hypothyroidism, LDL: 4.0 +/- 0.6, HDL: 3.6 +/- 0.4, N = 8). In ethanol-treated rats, transfer of surface lipids was similar to controls. |
| Transfer of plasma cholesterol and atherosclerosis Mezdour, H., G. Monte, et al. (1994), Ann Biol Clin (Paris) 52(2): 95-102. Abstract: Transfer processes in plasma are determinant in cholesterol metabolism. In many species, including man, there is an alternative route for the disposal of cholesteryl esters (CE) in HDL via transfer to VLDL in exchange for triglycerides (TG), a process dependent on a hydrophobic 74 kDa glycoprotein called cholesteryl ester transfer protein (CETP). In vivo, cholesteryl esters transferred from HDL will contribute to LDL, to which VLDL is converted. Although the prevention of CE accumulation in HDL may enhance the ability of HDL to take up more cholesterol from tissues, high rates of transfer may also increase the risk for atheroma by increasing formation of atherogenic lipoproteins. Conversely, CE retained within HDL, if returned directly to the liver, would be expected to be beneficial. Moreover, in most conditions predisposing to atheroma, CETP activity is raised; whereas species with low or absent CETP activity are at low risk for atherosclerosis. |
| Transferrin, cholesterol and aluminium in Alzheimer's disease Corrigan, F. M., J. S. Crichton, et al. (1992), Clin Chim Acta 211(1-2): 121-3. |
| Transformation of mouse peritoneal macrophages to foam cells in intraperitoneal injection of low density lipoproteins, cholesterol and its oxidized products Dushkin, M. I. and M. V. Ivanova (1993), Patol Fiziol Eksp Ter(2): 9-11. Abstract: To investigate the possibility of macrophage transformation to foam cells in vivo, the authors studied 14C-oleate incorporation into cellular cholesterol esters (CES) and the content of free cholesterol (CS) and CES in mouse peritoneal macrophages harvested 24 hours after intraperitoneal injection of native low density lipoproteins (LDL), acetylated LDL (acetyl-LDL), purified CS and CS autooxidated at 60 degrees C for a month. The rate of 14C-oleate incorporation into CES and the content of CES in the macrophages increased in relation to CS levels in the preparations and the nature of the injected agents. Injection of acetyl-LDL (2 mg CS/18 g body weight) and oxidized CS (1 mg/18 g body weight) caused a 10-fold increase of 14C-oleate incorporation into CES and a 60-fold increase of CES concentrations in the macrophages, which was evidence of their transformation to foam cells. The model of obtaining foam cells in vivo may be used in the study of atherogenesis. |
| Transforming growth factor beta1 decreases cholesterol supply to mitochondria via repression of steroidogenic acute regulatory protein expression Brand, C., N. Cherradi, et al. (1998), J Biol Chem 273(11): 6410-6. Abstract: Transforming growth factor-betas (TGF-betas) constitute a family of dimeric proteins that affect growth and differentiation of many cell types. TGF-beta1 has also been proposed to be an autocrine regulator of adrenocortical steroidogenesis, acting mainly by decreasing the expression of cytochrome P450c17. Here, we demonstrate that TGF-beta1 has a second target in bovine adrenocortical cells, namely the steroidogenic acute regulatory protein (StAR). Indeed, supplying cells with steroid precursors revealed that TGF-beta1 inhibited two steps in the steroid synthesis pathway, one prior to pregnenolone production and another corresponding to P450c17. More specifically, TGF-beta1 inhibited pregnenolone production but neither the conversion of 25-hydroxycholesterol to pregnenolone nor P450scc activity. Thus, TGF-beta1 must decrease the cholesterol supply to P450scc. We therefore examined the effect of TGF-beta1 on the expression of StAR, a mitochondrial protein implicated in intramitochondrial cholesterol transport. TGF-beta1 decreased the steady state level of StAR mRNA in a time- and concentration-dependent manner. This inhibition occurs at the level of StAR transcription and depends on RNA and protein synthesis. It is likely that the TGF-beta1-induced decrease of StAR expression that we report here may be expanded to other steroidogenic cells in which a decrease of cholesterol accessibility to P450scc by TGF-beta1 has been hypothesized. |
| Transforming growth factor-beta up-regulates low density lipoprotein receptor-mediated cholesterol metabolism in vascular smooth muscle cells Nicholson, A. C. and D. P. Hajjar (1992), J Biol Chem 267(36): 25982-7. Abstract: The effects of transforming growth factor-beta (TGF-beta) on low density lipoprotein (LDL) receptor-mediated cholesterol metabolism were evaluated in vascular smooth muscle cells. TGF-beta significantly increased the binding, uptake, and degradation of 125I-LDL. This increase was paralleled by an increase in LDL receptor mRNA steady state levels and an increase in cholesterol esterification. The increase in LDL cholesterol metabolism was independent of proliferation. LDL receptor expression in response to TGF-beta was not affected by coincubation with an antibody against platelet-derived growth factor or by cyclooxygenase inhibitors in arterial smooth muscle cells, suggesting that TGF-beta's effect was not mediated through platelet-derived growth factor or prostaglandins, as demonstrated in other cell systems. However, coincubation with pertussis toxin abrogated the effect of TGF-beta on LDL receptor expression, suggesting that a pertussis toxin-sensitive G-protein may be involved in the signal transduction pathway. These results are discussed in terms of their potential effects on cellular cholesterol trafficking. |
| Transforming growth factor-beta1 gene and protein expression associated with atherogenesis of cholesterol-fed rabbits Chen, Y. L., H. W. Wu, et al. (2000), Histol Histopathol 15(2): 421-8. Abstract: Transforming growth factor-beta1 (TGF-1beta) has been shown to modulate both cell proliferation and the synthesis of extracellular matrix by vascular cells. This study was aimed to establish the temporal correlation between TGF-beta1 expression, the expression of the extracellular matrix protein fibronectin, and plaque development during atherogenesis of hypercholesterolemic rabbits. New Zealand White rabbits were fed with 2% cholesterol-supplemented chow for 1 week, 2 weeks, 3 weeks or 6 weeks. TGF-beta1 mRNA and protein expression was examined in serial sections of aorta by in situ hybridization and immunohistochemistry. Fibronectin expression was examined by immunohistochemistry. In the control and 1-week feeding group, the expression of TGF-beta1 mRNA and protein was not apparent. In 2-week feeding group, intimal thickening was detected in which TGF-beta1 mRNA and protein were not clearly observed, either. The 3-week and 6-week feeding groups exhibited fatty streaks in which TGF-beta1 mRNA and protein expression markedly increased as feeding proceeded. Cell type-specific staining indicated that TGF-beta1 was expressed by macrophages as well as smooth muscle cells of the fatty streaks. Immunostaining of fibronectin detected low expression levels in control, 1-week and 2-week feeding groups with pronounced upregulation in the thickened intima and the proximal media in 3-week and 6-week feeding groups. These results implicate a role for TGF-beta1 in modulating fatty streak formation and the synthesis of extracellular protein fibronectin during plaque development. |
| Transgenic expression of cholesterol-7-alpha-hydroxylase prevents atherosclerosis in C57BL/6J mice Miyake, J. H., X. T. Duong-Polk, et al. (2002), Arterioscler Thromb Vasc Biol 22(1): 121-6. Abstract: C57BL/6J mice are susceptible to atherosclerosis when fed a diet consisting of fat, cholesterol, and taurocholate. The susceptibility to diet-induced atherosclerosis is linked to a reduction in plasma high density lipoprotein (HDL). Diet-induced reduction of plasma HDL shows a physiological and a genetic correlation with repression of cholesterol-7-alpha-hydroxylase, the liver-specific enzyme that regulates the conversion of cholesterol into bile acids. To examine the hypothesis that the repression of cholesterol-7-alpha-hydroxylase is responsible for initiating the metabolic alterations leading to the formation of atherosclerosis and gallstones, we determined whether constitutive transgenic expression of cholesterol-7-alpha-hydroxylase in C57BL/6J mice would confer resistance to these 2 common human diseases. When fed the atherogenic diet, nontransgenic littermates, but not cholesterol-7-alpha-hydroxylase transgenic mice, accumulated cholesterol and cholesterol esters in their livers and plasma. Although the atherogenic diet caused a marked decrease in plasma HDL cholesterol in nontransgenic mice, HDL levels in transgenic mice remained relatively unchanged. Moreover, the ability of cholesterol-7-alpha-hydroxylase transgenic mice to maintain cholesterol and lipoprotein homeostasis completely prevented the formation of atherosclerosis and gallstones. These data establish the integral role that cholesterol-7-alpha-hydroxylase has in maintaining hepatic cholesterol homeostasis and, thus, in the susceptibility to the formation of gallstones and atherosclerosis. |
| Transgenic mice expressing both human apolipoprotein B and human CETP have a lipoprotein cholesterol distribution similar to that of normolipidemic humans Grass, D. S., U. Saini, et al. (1995), J Lipid Res 36(5): 1082-91. Abstract: Transgenic mice expressing both human apolipoprotein (apo) B and human cholesteryl ester transfer protein (CETP) have been developed. When fed a normal mouse chow diet, the apoB/CETP double transgenic animals had threefold higher serum CETP activity than humans and had human apoB levels that were similar to those of normolipidemic humans. When compared with nontransgenic mice, the total serum cholesterol levels in the female apoB/CETP transgenic animals were increased significantly. Serum HDL cholesterol levels were decreased significantly in both male and female apoB/CETP transgenic animals. The percentages of the total cholesterol within the HDL, LDL, and VLDL fractions of the apoB/CETP animals were approximately 30%, 65%, and 5%, respectively, similar to the distribution of cholesterol in the plasma of normolipidemic humans. Thus, by expressing both human apoB and human CETP, the lipoprotein cholesterol distribution in the serum of a chow-fed mouse was transformed into one that resembles a human profile. |
| Transgenic mice expressing human phospholipid transfer protein have increased HDL/non-HDL cholesterol ratio Albers, J. J., A. Y. Tu, et al. (1996), Int J Clin Lab Res 26(4): 262-7. Abstract: The role of plasma phospholipid transfer protein (PLTP) in lipoprotein metabolism is poorly understood. In vitro studies suggest that PLTP influences HDL size and composition and transfers phospholipids among lipoproteins. To provide an in vivo model for studies of PLTP physiology, transgenic mice that express human PLTP were generated. Human PLTP transcripts were detected in total RNA from adipose tissue, lung, heart, and spleen of the two distinct lines (A and C) of transgenic mice. Despite minimal expression of human PLTP in the liver of these transgenic mice and similar plasma phospholipid transfer activity in transgenic and non-transgenic mice (19.1 +/- 3.1 vs 18.9 +/- 2.7 mumol/ml/h), differences in lipoprotein levels were observed between transgenic and control mice receiving the same chow diet. Male transgenic mice of line C had significantly higher HDL cholesterol than control mice (76.4 +/- 4.6 vs 71.9 +/- 7.0 mg/dl, p < 0.05) and the male transgenic mice of lines A and C had a significantly lower non-HDL cholesterol (15.1 +/- 4.1 and 15.6 +/- 4.7 vs 20.9 +/- 5.5 mg/dl, P < 0.01 and P < 0.02) and a significantly higher HDL cholesterol/non-HDL cholesterol ratio than the control mice (5.3 +/- 1.3 and 5.5 +/- 2.2 vs 3.9 +/- 1.9 mg/dl, P < 0.01 and P < 0.02). Female mice from transgenic line C had higher HDL cholesterol than control mice (64.6 +/- 4.8 vs 57.4 +/- 5.1 mg/dl, P < 0.01) while female mice from line A tended to have higher HDL cholesterol/non-HDL cholesterol ratio than control mice (5.5 +/- 3.7 vs 3.8 +/- 1.4). These observations suggest that expression of PLTP in peripheral tissues play an important role in lipoprotein metabolism. Expression of human PLTP produced a more favorable lipoprotein profile and thus, enhanced expression of PLTP could potentially retard atherosclerosis. |
| Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT) in mice does not increase aortic cholesterol deposition Furbee, J. W., Jr. and J. S. Parks (2002), Atherosclerosis 165(1): 89-100. Abstract: Results from several atherosclerosis studies using morphometric procedures have proven controversial with regard to whether over-expression of human LCAT in transgenic (Tg) mice is atherogenic. The purpose of the present study was to determine the effect of 10-fold over-expression of human LCAT on aortic free and esterified cholesterol (EC) deposition as well as plasma lipoprotein cholesteryl ester (CE) fatty acid composition in mice fed an atherogenic diet containing cholic acid. C57Bl/6 (control) and human LCAT-Tg mice were fed chow or an atherogenic diet (15% of calories from palm oil, 1.0% cholesterol and 0.5% cholic acid) for 24 weeks before measurement of aortic cholesterol content. Compared with the chow diet, control and LCAT-Tg mice fed the atherogenic diet had a 2-fold increase in plasma total, free and EC, a 7-fold increase in plasma apoB lipoprotein cholesterol, and a 40-50-fold increase in hepatic cholesterol content. The aortic EC content was increased in control (0.7 vs. 1.2 mg/g protein) and LCAT-Tg (0.3 vs. 1.5 mg/g protein) mice fed the atherogenic diet compared with those consuming the chow diet; however, there was no difference in aortic free (14.4+/-6.8 vs. 18.5+/-7.7 mg/g protein) or esterified (1.2+/-1.0 vs. 1.5+/-1.2 mg/g protein) cholesterol content between atherogenic diet-fed control and LCAT-Tg mice, respectively. LCAT-Tg mice fed the atherogenic diet had a 2-fold increase in the ratio of saturated+monounsaturated to polyunsaturated CE species in plasma apoB lipoproteins compared with control mice (9.4+/-2.4 vs. 4.9+/-0.7). We conclude that over-expression of human LCAT in Tg mice fed an atherogenic diet containing cholic acid does not result in increased aortic cholesterol deposition compared with control mice, even though the CE fatty acid saturation index of plasma apoB lipoproteins was doubled. |
| Transgenic rabbits expressing human apolipoprotein(a) develop more extensive atherosclerotic lesions in response to a cholesterol-rich diet Fan, J., H. Shimoyamada, et al. (2001), Arterioscler Thromb Vasc Biol 21(1): 88-94. Abstract: High lipoprotein(a) Lp(a) levels constitute an independent risk factor for the development of atherosclerosis. However, the relationship between Lp(a) and atherosclerosis is not fully understood. To examine the effect of Lp(a) on the development of atherosclerosis, we studied transgenic rabbits expressing human apolipoprotein(a) apo(a), which was assembled into Lp(a) in the plasma. Human apo(a) transgenic rabbits fed a 0.3% cholesterol diet for 16 weeks had more extensive atherosclerotic lesions than did nontransgenic rabbits, although the cholesterol levels in the plasma of both groups were similarly elevated. Compared with the lesions in control rabbits, the areas of the atherosclerotic lesions in human apo(a) transgenic rabbits were significantly increased in the aorta, the iliac artery, and the carotid artery. Furthermore, human apo(a) transgenic rabbits on a cholesterol-rich diet had a greater degree of coronary atherosclerosis than did control rabbits. Immunohistochemical analysis revealed that human apo(a) was frequently deposited in the atherosclerotic lesions of transgenic rabbits. We conclude that Lp(a) may have proatherogenic effects in the setting of a cholesterol-rich diet in transgenic rabbits. |
| Transient experimental anemia in cholesterol-fed rabbits induces systemic overexpression of the reticulocyte-type 15-lipoxygenase and protects from aortic lipid deposition Trebus, F., D. Heydeck, et al. (2002), Prostaglandins Leukot Essent Fatty Acids 67(6): 419-28. Abstract: Oxidative modification of low-density lipoprotein has been implicated in atherogenesis and the lipid peroxidizing enzyme 12/15-lipoxygenase (12/15-LOX) was suggested to be involved. For this study, we induced a strong and long-lasting systemic overexpression of the 15-LOX, in female New Zealand White rabbits by transient experimental anemia. After the hematopoietic parameters had returned to normal, these animals and age-matched controls were fed a lipid-rich Western-type diet for 10 weeks. Analyzing the lipid deposition in the aortic wall, we found that the 15-LOX overexpressing rabbits deposited significantly (P<0.01) less cholesteryl linoleate in the thoracic aorta than the corresponding controls. Similar results were obtained when free cholesterol and cholesteryl oleate were quantified. However, in the aortic arch where lipid deposition was much more severe a similar trend was observed, but the effects were not significant any more. Comparative determination (lipoxygenase overexpressing vs. control animals) of various plasma parameters as well as histological inspections of major organs did not reveal any indications for major organ malfunction. These data suggest that transient experimental anemia, which is accompanied by a long-lasting overexpression of the reticulocyte-type 15-LOX protects cholesterol-fed rabbits from lipid deposition in the aortic wall. |
| Transient reductions in serum cholesterol after renal transplantation Kasiske, B. L. and K. L. Heim-Duthoy (1992), Am J Kidney Dis 20(4): 387-93. Abstract: Declines in serum cholesterol have been reported in patients with altered immune system activity. However, the frequency and clinical significance of transient reductions in serum cholesterol after renal transplantation are unknown. In the present retrospective study, we examined the frequency and clinical setting of reduced serum cholesterol (< or = 4.40 mmol/L 170 mg/dL) in patients who each had 28 +/- 7 (total, 1,110) cholesterol determinations during the first year posttransplant. Reduced cholesterol was found on at least one occasion in 26 of 40 (65%) patients. Ninety-two percent (119/129) of the reduced cholesterol values occurred in one of three clinical settings: (1) within 10 days after transplantation, (2) within 6 weeks before or after the onset of acute rejection, or (3) within 6 weeks before or after the onset of a cytomegalovirus infection (CMV). Multiple linear regression analysis showed that the relationship between reductions in cholesterol associated with acute rejection was independent of CMV and the type of immunosuppression (one half of the patients were treated with cyclosporine CSA). The fact that serum albumin was reduced during CMV, but not during acute rejection, suggested that reduced cholesterol associated with rejection was relatively specific, and was not caused by a generalized leak of plasma proteins or by poor nutrition. Thus, during the first year posttransplant, reductions in serum cholesterol are most often associated with acute rejection episodes and/or CMV.(ABSTRACT TRUNCATED AT 250 WORDS) |