Biomedical subjects

L B Nielsen

Publications and source records attributed to L B Nielsen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice.

A deficiency in microsomal triglyceride transfer protein (MTP) causes the human lipoprotein deficiency syndrome abetalipoproteinemia. However, the role of MTP in the assembly and secretion of VLDL in the liver is not precisely understood. It is not clear, for instance, whether MTP is required to move the bulk of triglycerides into the lumen of the endoplasmic reticulum (ER) during the assembly of VLDL particles. To define MTP's role in hepatic lipoprotein assembly, we recently knocked out the mouse MTP gene (Mttp). Unfortunately, achieving our objective was thwarted by a lethal embryonic phenotype. In this study, we produced mice harboring a "floxed" Mttp allele and then used Cre-mediated recombination to generate liver-specific Mttp knockout mice. Inactivating the Mttp gene in the liver caused a striking reduction in VLDL triglycerides and large reductions in both VLDL/LDL and HDL cholesterol levels. The Mttp inactivation lowered apo B-100 levels in the plasma by >95% but reduced plasma apo B-48 levels by only approximately 20%. Histologic studies in liver-specific knockout mice revealed moderate hepatic steatosis. Ultrastructural studies of wild-type mouse livers revealed numerous VLDL-sized lipid-staining particles within membrane-bound compartments of the secretory pathway (ER and Golgi apparatus) and few cytosolic lipid droplets. In contrast, VLDL-sized lipid-staining particles were not observed in MTP-deficient hepatocytes, either in the ER or in the Golgi apparatus, and there were numerous cytosolic fat droplets. We conclude that MTP is essential for transferring the bulk of triglycerides into the lumen of the ER for VLDL assembly and is required for the secretion of apo B-100 from the liver.

Alleles↗

PubMed1998

Apolipoprotein B gene expression in a series of human apolipoprotein B transgenic mice generated with recA-assisted restriction endonuclease cleavage-modified bacterial artificial chromosomes. An intestine-specific enhancer element is located between 54 and 62 kilobases 5' to the structural gene.

Prior studies have established that the expression of the human apolipoprotein B (apoB) gene in the intestine is dependent on DNA sequences located a great distance from the structural gene. To identify the location of those sequences, we used recA-assisted restriction endonuclease (RARE) cleavage to truncate the 5'- or 3'-flanking sequences from a 145-kilobase (kb) bacterial artificial chromosome spanning the entire human apoB gene. Seven RARE cleavage- modified bacterial artificial chromosomes with different lengths of flanking sequences were used to generate transgenic mice. An analysis of those mice revealed that as little as 1.5 kb of 3' sequences or 5 kb of 5' sequences were sufficient to confer apoB expression in the liver. In contrast, apoB gene expression in the intestine required DNA sequences 54-62 kb 5' to the structural gene. Those sequences retained their ability to direct apoB expression in the intestine when they were moved closer to the gene. These studies demonstrate that the intestinal expression of the apoB gene is dependent on DNA sequences located an extraordinary distance from the structural gene and that the RARE cleavage/transgenic expression strategy is a powerful approach for analyzing distant gene-regulatory sequences.

Animals↗

PubMed1998

Genes for apolipoprotein B and microsomal triglyceride transfer protein are expressed in the heart: evidence that the heart has the capacity to synthesize and secrete lipoproteins.

BACKGROUND: Expression of both the apolipoprotein B (apoB) gene and the microsomal triglyceride transfer protein (MTP) gene is required for the assembly and secretion of triglyceride-rich lipoproteins in the liver and intestine. Both genes have been assumed to be silent in the heart. METHODS AND RESULTS: Northern blot and RNase protection analyses showed that the apoB and MTP genes were expressed in the hearts of mice and humans. In situ hybridization studies revealed that the apoB mRNA was produced in cardiac myocytes. Electron microscopy of human cardiac myocytes revealed lipid-staining particles of relatively small diameter (approximately 250 A) within the Golgi apparatus. CONCLUSIONS: These studies strongly suggest that the heart synthesizes and secretes apoB-containing lipoproteins.

Animals↗

PubMed1998

Expression of large genomic clones in transgenic mice: new insights into apolipoprotein B structure, function and regulation.

Extensive manipulation of the apolipoprotein B gene in yeast and bacterial artificial chromosome clones and subsequent expression of these clones in transgenic mice have provided fresh insights into several aspects of apolipoprotein B biology, including the identification of sequences important for lipoprotein (a) assembly, the demonstration that intestinal expression of apolipoprotein B is controlled by DNA sequences > 50 kb from the gene, and the extraordinary finding that apolipoprotein B is expressed in the heart.

Animals↗

PubMed1998

Increased degradation of lipoprotein(a) in atherosclerotic compared with nonlesioned aortic intima-inner media of rabbits: in vivo evidence that lipoprotein(a) may contribute to foam cell formation.

To investigate a potential role of lipoprotein(a) [Lp(a)] in foam cell formation, we have measured the degradation rates of Lp(a) and LDL in the rabbit aorta in vivo. Lp(a) (or LDL) was labeled with both 113I-TC and 125I and injected into 17 rabbits with extensive aortic atherosclerosis and into 16 rabbits without atherosclerosis. As the protein moiety of the doubly labeled lipoproteins is degraded, 131I-TC is trapped in the cell, whereas 125I diffuses out of the cell. Twenty-four hours after injection, 12 samples of the aorta and biopsies from 9 other tissues were removed. The degradation rate of Lp(a) (percent of plasma pool per gram tissue per day) was less than that of LDL in the adrenals and in the intestine. In contrast, degradation rates of Lp(a) and LDL were similar in liver, spleen, kidney, heart, lung, skeletal muscle, and adipose tissue. In nonlesioned aortic intima-inner media, the degradation rate of Lp(a) was 39% of that of LDL (t test: P <.05 in aortic arch and thoracic aorta), whereas the degradation rates of Lp(a) and LDL were similar in atherosclerotic aortic intima-inner media. Lp(a) degradation rates were markedly increased in atherosclerotic compared with nonlesioned aortic intima-inner media: 28.2+/-9.2 x 10(-7)% and 5.0+/-0.6 x 10(-7)% of the plasma pool per gram tissue per day in the intima-inner media of the proximal segment of atherosclerotic and nonlesioned aorta, respectively (t test: P <.01). These results suggest that the metabolism of Lp(a) is different from that of LDL in nonlesioned arterial intima, possibly reflecting that Lp(a) is degraded by LDL receptors in arterial intima less efficiently than LDL. The results also indicate that the degradation rate of Lp(a) is markedly increased in atherosclerotic lesions of rabbits, supporting the idea that Lp(a) contributes to foam cell formation during the development of atherosclerosis.

Animals↗

PubMed1998

Chylomicron-sized lipid particles are formed in the setting of apolipoprotein B deficiency.

The mechanisms for packaging large quantities of neutral lipids into apolipoprotein (apo) B-containing lipoproteins (chylomicrons or VLDL) are incompletely understood. However, several lines of evidence have suggested that the addition of core lipids to apoB to form a lipoprotein particle within the endoplasmic reticulum (ER) may involve two steps: first, the addition of small amounts of core lipids to membrane-bound apoB, generating a lipid-poor, small apoB-containing particle, and second, the fusion of that particle with a larger, independently formed triglyceride-rich and apoB-free "lipid particle." We sought to test this two-step hypothesis of apoB core lipidation by using electron microscopy to compare chylomicron assembly in mice that are genetically deficient in the ability to synthesize apoB in the intestine to control mice. In 19-day gestational mice (fasting setting) that were deficient in intestinal apoB synthesis, chylomicron-sized lipid particles in the lumen of the enterocyte ER were even more abundant and were 2- to 3-fold larger than those in the enterocytes of normal control mice. However, there were fewer lipid-staining particles in the Golgi apparatus, and many fewer particles in the extracellular space, compared with normal control mice. In both types of newborn suckling mice, much larger lipid particles were assembled within the lumen of the ER. They were however, less abundant and rarely reached the Golgi apparatus in fatty enterocytes of intestines deficient in apoB synthesis. These observations provide in vivo evidence that chylomicron formation could involve the synthesis of apoB-free triglyceride-rich particles within the endoplasmic reticulum (ER) lumen, and that the transport of these lipid particles out of the ER to Golgi apparatus and interstitium is facilitated by the acquisition of apoB.

Animals↗

PubMed1997

Human apolipoprotein B transgenic mice generated with 207- and 145-kilobase pair bacterial artificial chromosomes. Evidence that a distant 5'-element confers appropriate transgene expression in the intestine.

We reported previously that approximately 80-kilobase pair (kb) P1 bacteriophage clones spanning either the human or mouse apoB gene (clones p158 and p649, respectively) confer apoB expression in the liver of transgenic mice, but not in the intestine. We hypothesized that the absence of intestinal expression was due to the fact that these clones lacked a distant DNA element controlling intestinal expression. To test this possibility, transgenic mice were generated with 145- and 207-kb bacterial artificial chromosomes (BACs) that contained the human apoB gene and more extensive 5'- and 3'-flanking sequences. RNase protection, in situ hybridization, immunohistochemical, and genetic complementation studies revealed that the BAC transgenic mice manifested appropriate apoB gene expression in both the intestine and the liver, indicating that both BACs contained the distant intestinal element. To determine whether the regulatory element was located 5' or 3' to the apoB gene, transgenic mice were generated by co-microinjecting embryos with p158 and either the 5'- or 3'-sequences from the 145-kb BAC. Analysis of these mice indicated that the apoB gene's intestinal element is located 5' to the structural gene. Cumulatively, the transgenic mouse studies suggest that the intestinal element is located between -33 and -70 kb 5' to the apoB gene.

Animals↗

PubMed1997

Construction of two near-kilobase resolution restriction maps of the 5' regulatory region of the human apolipoprotein B gene by quantitative DNA fiber mapping (QDFM).

Quantitative DNA fiber mapping (QDFM) is a high-resolution technique for physical mapping of DNA. The method is based on hybridization of fluorescently labeled DNA probes to individual DNA molecules stretched on a chemically modified glass surface. We now demonstrate and validate a rapid QDFM-based approach for the mapping of multiple restriction sites and precise localization of restriction fragments in large genomic clones. Restriction fragments of a 70-kb P1 clone (P1-70) containing the 5' region of the human apolipo-protein B gene (APOB) were subcloned and mapped along straightened P1-70 DNA molecules. Multicolor fluorescence in situ hybridization (FISH) and digital image analysis allowed us to rapidly position 29 restriction fragments, ranging in size from 0.5 kb to 8 kb, and to map 43 restriction sites. The restriction map obtained by QDFM was in excellent agreement with information obtained by RecA-assisted restriction endonuclease (RARE) cleavage, long-range PCR, and DNA sequence analyses of the P1-70 clone. These data demonstrate that QDFM is a rapid, reliable method for detailed restriction site-mapping of large DNA clones.

Apolipoproteins B↗

PubMed1997

In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima.

The aim of this study was to compare the atherogenic potential of lipoprotein(a) [Lp(a)] and LDL by measuring the intimal clearance of these two plasma lipoproteins in the atherosclerotic intima of the human carotid artery in vivo. Autologous 131I-Lp(a) and 125I-LDL were mixed and reinjected intravenously 3 hours before elective surgical removal of the arterial intima in four patients. The intimal clearance of Lp(a) and LDL was 229+/-48 and 405+/-127 nL/cm2 per hour, respectively (paired t test; P=.12). The mass accumulation of Lp(a) (114+/-32 ng/cm2 per hour) was on average one 15th that of LDL (paired t test; P=.06), mainly reflecting a low plasma concentration of Lp(a) compared with LDL in the human subjects studied. In accordance with our previous observation in rabbits, there was a positive association between the intimal clearance of LDL and that of Lp(a) (r=.97, P=.03). Accordingly, high plasma levels of Lp(a) may share with LDL the potential for causing lipid accumulation in the arterial intima in humans.

Aged↗

PubMed1996

Oxidation of plasma low-density lipoprotein accelerates its accumulation and degradation in the arterial wall in vivo.

BACKGROUND: The aim of the present study was to investigate whether oxidized LDL (ox-LDL) in the arterial intima could be derived from LDL already oxidized in plasma. METHODS AND RESULTS: Rabbits received an intravenous injection of 125I-labeled normal LDL (N-LDL) mixed with 131I-labeled LDL that had been mildly oxidized through exposure to Cu2+. The aortic accumulation of undegraded labeled LDL was expressed as plasma equivalents and cakulated as radioactivity in the intima/inner media (cpm/cm2) divided by the time-averaged concentration of radioactivity in plasma (cpm/nL): for the thoracic aorta, the accumulation of undegraded ox-LDL in the intima/ inner media exceeded that of undegraded N-LDL by 286% (n = 6, P < .04), 863% (n = 7, P < .02), and 364% (n = 8, P < .01) after 1, 3, and 24 hours of exposure, respectively. There was a strong positive association between the extent of oxidation and the excess accumulation of undegraded ox-LDL compared with N-LDL (thoracic aorta; 3 hours of exposure: r = .97, n = 14, P < .00001). To measure degradation of N-LDL and ox-LDL, 125I-LDL labeled with 131I-tyramine cellobiose was injected intravenously 24 hours before the aortic intima/inner media was removed: for the thoracic aorta, the accumulation of degradation products from ox-LDL (n = 6) exceeded that from N-LDL (n = 6) by 301% (P < .04). CONCLUSIONS: The present data suggest a novel mechanism: mildly oxidized LDL may circulate in plasma for a period sufficiently long to enter, accumulate, and be degraded in the arterial intima in preference to N-LDL.

Animals↗

PubMed1996

Preferential influx and decreased fractional loss of lipoprotein(a) in atherosclerotic compared with nonlesioned rabbit aorta.

The aim was to investigate the atherogenic potential of lipoprotein(a) (Lp(a)) and to further our understanding of the atherogenic process by measuring rates of transfer into the intima-inner media (i.e., intimal clearance) and rates of loss from the intima-inner media (i.e., fractional loss) of Lp(a) and LDL using cholesterol-fed rabbits with nonlesioned (n = 13) or atherosclerotic aortas (n = 12). In each rabbit, 131I-Lp(a) (or 131I-LDL) was injected intravenously 26 h before and 125I-Lp(a) (or 125I-LDL) 3 h before the aorta was removed and divided into six consecutive segments of similar size. The intimal clearance of Lp(a) and LDL was similar and markedly increased in atherosclerotic compared with nonlesioned aortas (ANOVA, effect of atherosclerosis: P < 0.0001). Fractional losses of labeled Lp(a) and labeled LDL in atherosclerotic aorta were on average 25 and 43%, respectively, of that in nonlesioned aortas (ANOVA, effect of atherosclerosis: P < 0.0001). Fractional loss of Lp(a) was 73% of that of LDL (ANOVA, effect of type of lipoprotein: P = 0.07). These data suggest that the development of atherosclerosis is associated with increased influx as well as decreased fractional loss of Lp(a) and LDL from the intima. Accordingly, Lp(a) may share with LDL the potential for causing atherosclerosis.

Analysis of Variance↗

PubMed1996

Transfer of low density lipoprotein into the arterial wall and risk of atherosclerosis.

The aim of the review is to summarize the present knowledge on determinants of transfer of low density lipoprotein (LDL) into the arterial wall, particularly in relation to the risk of development of atherosclerosis. The flux of LDL into the arterial wall (in moles of LDL per surface area per unit of time) has two major determinants, i.e. the LDL concentration in plasma and the arterial wall permeability. LDL enters the arterial wall as intact particles by vesicular ferrying through endothelial cells and/or by passive sieving through pores in or between endothelial cells. Estimates in vivo of the LDL permeability of a normal arterial wall vary between 5 and 100 nl/cm2/h. In laboratory animals, the regional variation in the arterial wall permeability predicts the pattern of subsequent dietary induced atherosclerosis. Moreover, mechanical or immunological injury of the arterial wall increases the LDL permeability and is accompanied by accelerated development of experimental atherosclerosis. This supports the idea that an increased permeability to LDL, like an increased plasma LDL concentration, increases the risk of atherosclerosis. Hypertension, smoking, genetic predisposition, atherosclerosis, and a small size of LDL may all increase the arterial wall permeability to LDL and in this way increase the risk of accelerated development of atherosclerosis. The hypothesis that atherosclerosis risk can be reduced by improving the barrier function of the arterial wall towards the entry of LDL remains to be investigated; agents which directly modulate the LDL permeability of the arterial wall in vivo await identification.

Animals↗

PubMed1996

Specific accumulation of lipoprotein(a) in balloon-injured rabbit aorta in vivo.

To explore whether lipoprotein(a), Lp(a), may accumulate preferentially to LDL in the arterial wall at sites of injury, cholesterol-fed rabbits were injected intravenously with radiolabeled Lp(a) and/or LDL 3.1 +/- 0.1 days (mean +/- SEM, n = 30) after a balloon injury of the thoracic aorta. After 5 to 10 minutes' exposure to labeled lipoproteins, more labeled LDL than labeled Lp(a) was recovered in the intima-inner media of the balloon-injured segment (n = 9; paired t test, P < .0001); however, the amount of tightly bound labeled lipoprotein was similar for the two lipoprotein fractions. In the second set of experiments, 131I-Lp(a) (or 131I-LDL) was injected 26 hours before and 125I-Lp(a) (or 125I-LDL) 3 hours before the aorta was removed. Permeability and fractional loss of labeled Lp(a) (n = 8) versus LDL (n = 7) in the balloon-injured aortic intima-inner media were: permeability, 0.46 +/- 0.10 microL/cm2 per hour versus 1.41 +/- 0.32 microL/cm2 per hour (nonpaired t test, P < .0001); and fractional loss, 0.12 +/- 0.02 h-1 versus 0.44 +/- 0.05 h-1 (nonpaired t test, P = .0001), respectively. Finally, after 23 hours' exposure to labeled lipoproteins, the total accumulation and the amount of tightly bound labeled Lp(a) in the balloon-injured intima-inner media were, respectively, 174% (n = 6; ANOVA, P = .03) and 256% ANOVA, P = .005) of the values for labeled LDL. For labeled Lp(a) in the balloon-injured compared with the normal aortic intima-inner media, the recovery after 5 to 10 minutes, the permeability, and the accumulation after 23 hours were all increased, whereas the fractional loss was unchanged. These data suggest that the accumulation of Lp(a) is much larger in injured vessels than in normal vessels. Moreover, the data support the idea of a specific accumulation of Lp(a) compared with LDL in injured vessels.

Animals↗

PubMed1995

Replacement of dietary saturated fat with monounsaturated fat: effect on atherogenesis in cholesterol-fed rabbits clamped at the same plasma cholesterol level.

The aim was to compare the effect on atherogenesis of dietary monounsaturated and saturated fatty acids in cholesterol-clamped rabbits. To obtain an average plasma cholesterol concentration of 20 mmol/l in each rabbit during the 13-week cholesterol-feeding period, dietary cholesterol was adjusted weekly. The amount of fat fed daily was 10 g per rabbit in Expts A (n 23), C (n 36), and D (n 58) and 5 g per rabbit in Expt B (n 24). The source of monounsaturated fatty acids was olive oil in all four experiments. The source of saturated fatty acids was butter in Expt A, lard in Expt B, coconut oil in Expt C, and butter or lard in Expt D. Generally, olive oil-fed groups received more cholesterol and tended to have more cholesterol in VLDL and less in LDL compared with groups receiving saturated fat. Analysis of variance of the combined results of all four experiments showed that, in comparison with saturated fat, olive oil lowered aortic cholesterol by 13 (-9-30, 95% confidence interval) % in the aortic arch, and by 10 (-10-26) % in the thoracic aorta, which was not significant. In the comparison with olive oil, no differences in effects on aortic cholesterol content were detected between butter, lard and coconut oil. These findings do not support the view that replacement of dietary saturated fat with olive oil has a major impact on the development of atherosclerosis in addition to that accounted for by changes in plasma cholesterol levels.

Animals↗

PubMed1995

Transfer of lipoprotein(a) and LDL into aortic intima in normal and in cholesterol-fed rabbits.

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.

Animals↗

PubMed1994

An interview study of nurses' assessment and priority of post surgical pain experience.

Caring for patients in postoperative pain is an important part of clinical practice for nurses. Patients often fail to receive adequate pain relief which causes unnecessary pain experience. The aim of this study was to describe how nurses experience their clinical practice management with postoperative patients who experience pain. Eight nurses, practising in the postoperative care unit and surgical wards were interviewed. Data were gathered in unstructured interviews and analysed by means of a qualitative method. Six categories emerged: organising condition, perspective, attitude, knowledge, experience and assessment/priority. All the conditions are interrelated and influenced the nurses' handling of pain management in nursing practice. It appeared that these conditions reflected the nurses' possibilities of relieving patients' postoperative pain. An important element was the reflection of hospital management policy which makes the nurses, in spite of their desire to relieve the patients' pain, choose to have the attitude that the patient should be prepared to accept a little pain.

Adult↗

PubMed1994

Atherosclerosis and arterial influx of lipoproteins.

Accumulation of atherogenic lipoproteins in the arterial intima is a key event in the development of atherosclerosis. The likelihood of increased lipoprotein accumulation in the intima increases with increasing influx: arterial influx of lipoproteins is increased by increased arterial wall permeability, increased lipoprotein concentration in plasma, and by high blood pressure. On entrance into the arterial intima, lipoproteins can either efflux as intact particles, be retained in the intima, or be degraded by intimal cells. Increased degradation as well as increased retention of lipoproteins in the intima have both been associated with increased development of atherosclerosis. Therefore, low rates of efflux of intact particles, as appears to be the case for large particles like VLDL, IDL, and possibly lipoprotein (a) could potentially promote atherosclerosis.

Animals↗

PubMed1994

Aortic permeability to LDL during estrogen therapy. A study in normocholesterolemic rabbits.

17 beta-Estradiol has recently been found to inhibit atherogenesis by mechanisms that are in part independent of the estrogenic action on plasma lipoprotein levels. Since aortic permeability to low-density lipoprotein (LDL) in normocholesterolemic rabbits is a strong predictor for subsequent atherosclerosis during hypercholesterolemia, the present study investigated a possible influence of 17 beta-estradiol on aortic permeability to LDL. Twenty rabbits were initially ovariectomized and then fed a nonatherogenic diet for 10 weeks. One group of rabbits (n = 10) received 4 mg of 17 beta-estradiol orally per day; the other group (n = 10) received placebo. Serum concentrations of very-low-density lipoprotein cholesterol and triglycerides increased significantly more in the placebo group than in the estrogen group (P < .03), whereas there were no statistically significant differences between groups in LDL, high-density lipoprotein, or total cholesterol. At the end of the experiment, 125I-LDL was injected intravenously into each rabbit. Aortas were removed 3 hours later, and the aortic permeability to LDL was calculated from the radioactivity in the plasma and the aortic intima/inner media. The aortic permeability to LDL was virtually identical in the 17 beta-estradiol (31.6 +/- 7.2 nL.cm-2.h-1) and the placebo (36.9 +/- 7.9 nL.cm-2.h-1) groups (mean +/- SEM). The aortic cholesterol content was also similar in the two groups. These data suggest that the plasma lipid-independent antiatherogenic effect of estradiol is not mediated through an effect on aortic permeability to LDL but rather is related to the metabolism of the lipoproteins after they have entered the arterial wall.

Animals↗