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PubMed1988

Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I.

Serum PGI2 stabilizing factor (PSF) was purified from human serum to a single protein with a molecular weight of 28,000 D by SDS-PAGE. Analyses of NH2-terminal sequence (32 residues), COOH-terminal sequence (3 residues) and the composition of amino acids disclosed its homology with human apolipoprotein A-I (Apo A-I), a major apolipoprotein of HDL. Apolipoprotein A-II, C-I, C-II, C-III, D and E, as well as LDL, and VLDL did not possess this activity. The alpha-helix structure of Apo A-I is necessary for the binding of PGI2. HDL and nascent HDL reconstituted from Apo A-I and phospholipid significantly prolonged the half-life of PGI2. PGI2 stabilization by HDL and Apo A-I may be an important protective action against the accumulation of platelet thrombi at sites of vascular damage. The beneficial effect of HDL in the prevention of coronary artery disease may be partly due to this action.

Amino Acid Sequence↗
PubMed1997

In vivo metabolism of apo A-I and apo A-II in subjects with apo A-I(Lys107-->0) associated with reduced HDL cholesterol and Lp(AI w AII) deficiency.

Apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) represent 80 90% of the protein content of high density lipoproteins (HDL). Previously we have identified a Finnish family with an apo A-I variant (Lys107-->0) associated with reduced plasma HDL cholesterol level and decreased lipoprotein (Lp)(AI w AII) concentration compared to unaffected family members. To determine the in vivo metabolism of apo A-I and apo A-II in the carriers of apo A-I (Lys107-->0) variant we radioiodinated normal apo A-I with 125I and apo A-II with 131I and compared the kinetic data of two heterozygous apo A-I(Lysl07-->0) patients (HDL cholesterol leves 0.31 and 0.69 mmol/l) to that of eight normolipidemic, healthy control subjects. Plasma radioactivity curves of 125I-labelled normal apo A-I of the patients demonstrated accelerated clearance of apo A-I compared to control subjects. In the two patients the fractional catabolic rates (FCR) of apo A-I were 0.347/day and 0.213/day, respectively, while the mean FCR of apo A-I of the control subjects was 0.151 +/- 0.041/day. Similarly, the plasma decay curves of the 131I-labelled apo A-II showed more rapid clearance of apo A-II in the two patients than in control subjects. The FCR of apo A-II in the two patients were 0.470/day and 0.234/day, while the mean FCR of apo A-II in control subjects was 0.154 +/- 0.029/day. The calculated production rates of apo A-I were similar in patients and in control subjects, and the production rates of apo A-II were significantly higher in patients than in control subjects. Our results show that the Lp(AI w AII) deficiency in patients with the apo A-I(Lys107-->0) is associated with increased fractional catabolic rates of normal apo A-I and apo A-II, while the production rates of these apolipoproteins are normal (apo A-I) or slightly increased (apo A-II).

Apolipoprotein A-I↗
PubMed1995

Effect of bezafibrate on HDL with APO A-I and APO A-II and on HDL with APO A-I without APO A-II in hyperlipidaemic patients.

On the basis of apoprotein composition, high-density lipoprotein (HDL) particles may be subdivided into two main subpopulations defined by the presence in the lipoprotein molecule of apo A-I (Lp A-I) and of both apo A-I and apo A-II (Lp A-I:A-II). The effect of slow-release bezafibrate 400 mg a day on Lp A-I and Lp A-I: A-II was evaluated in 34 hyperlipidaemic patients (19 with hypercholesterolaemia and 15 with hypertriglyceridaemia). Seventeen patients on low-fat low-cholesterol diet only were taken as the reference group. In the reference group, no change in HDL-C, apo A-I, apo A-II, Lp A-I and Lp A-I:A-II occurred during the 3 months of observation. In patients on bezafibrate, HDL-C, apo A-I and apo A-II significantly increased. Lp A-I:A-II increased by 33% in hypercholesterolaemic and by 29% in hypertriglyceridaemic patients. Lp A-I decreased by 15% in hypercholesterolaemic patients and did not change significantly in hypertriglyceridaemic patients. This differential effect of bezafibrate on apo-A-defined HDL subpopulations in hypertriglyceridaemia and in hypercholesterolaemia is in accord with previous studies on the effect of the drug on HDL subfractions defined by their density.

Apolipoprotein A-I↗
PubMed2001

Enhanced fractional catabolic rate of apo A-I and apo A-II in heterozygous subjects for apo A-I(Zaragoza) (L144R).

We have recently reported a new apolipoprotein (apo) A-I variant (apo A-I(Zaragoza) L144R) in a Spanish family with HDL-C levels below the 5th percentile for age and sex and low apo A-I concentrations. All the apo A-I(Zaragoza) subjects were heterozygous and none of them showed evidence of coronary artery disease (CAD). Mean plasma HDL-C, apo A-I, and apo A-II levels were lower in apo A-I(Zaragoza) carriers as compared to control subjects (40, 60, and 50%, respectively). Lipid composition analysis revealed that apo A-I(Zaragoza) carriers had HDL particles with a higher percentage of HDL triglyceride and a lower percentage of HDL esterified cholesterol as compared to those of control subjects. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate of apo A-I(Zaragoza) carriers were normal. Apo A-I and apo A-II metabolic studies were performed on two heterozygous apo A-I(Zaragoza) carriers and on six control subjects. We used a primed constant infusion of [5,5,5-2H3]leucine and HDL apo A-I and apo A-II tracer/tracee ratios were determined by gas chromatography mass spectrometry and fitted to a monoexponential equation using SAAM II software. Both subjects carrying apo A-I(Zaragoza) variant showed mean apo A-I fractional catabolic rate (FCR) values more than two-fold higher than mean FCR values of their controls (0.470+/-0.0792 vs. 0.207+/-0.0635 x day(-1), respectively). Apo A-I secretion rate (SR) of apo A-I(Zaragoza) subjects was slightly increased compared with controls (17.32+/-0.226 vs. 12.76+/-3.918 mg x kg(-l) x day(-1), respectively). Apo A-II FCR was also markedly elevated in both subjects with apo A-I(Zaragoza) when compared with controls (0.366+/-0.1450 vs. 0.171+/-0.0333 x day(-1), respectively) and apo A-II SR was normal (2.31+/-0.517 vs. 2.1+/-0.684 mg x kg(-l) x day(-1), respectively). Our results show that the apo A-I(Zaragoza) variant results in heterozygosis in abnormal HDL particle composition and in enhanced catabolism of apo A-I and apo A-II without affecting significantly the secretion rates of these apolipoproteins and the LCAT activation.

Adult↗
PubMed2000

Effect of overexpression of human apo A-I in C57BL/6 and C57BL/6 apo E-deficient mice on 2 lipoprotein-associated enzymes, platelet-activating factor acetylhydrolase and paraoxonase. Comparison of adenovirus-mediated human apo A-I gene transfer and human apo A-I transgenesis.

Various mechanisms may contribute to the antiatherogenic potential of apolipoprotein A-I (apo A-I) and high density lipoproteins (HDLs). Therefore, the effect of adenovirus-mediated human apo A-I gene transfer or human apo A-I transgenesis on platelet-activating factor acetylhydrolase (PAF-AH) and arylesterase/paraoxonase (PON1) was studied in C57BL/6 and C57BL/6 apo E(-/-) mice. Human apo A-I transgenesis in C57BL/6 mice resulted in a 4.2-fold (P<0.0001) increase of PAF-AH and a 1.7-fold (P=0.0012) increase of PON1 activity. The apo E deficiency was associated with a 1.6-fold (P=0.008) lower PAF-AH and a 2.0-fold (P=0.012) lower PON1 activity. Human apo A-I transgenesis in C57BL/6 apo E(-/-)mice increased PAF-AH and PON1 activity by 2.1-fold (P=0.01) and 2.5-fold (P=0.029), respectively. After adenovirus-mediated gene transfer of human apo A-I into C57BL/6 apo E(-/-)mice, a strong correlation between human apo A-I plasma levels and PAF-AH activity was observed at day 6 (r=0.92, P<0.0001). However, PON1 activity failed to increase, probably as a result of cytokine-mediated inhibition of PON 1 expression. In conclusion, this study indicates that overexpression of human apo A-I increases HDL-associated PAF-AH activity. PON1 activity was also increased in human apo A-I transgenic mice, but not after human apo A-I gene transfer, a result that was probably related to cytokine production induced in the liver by the adenoviral vectors. Increased levels of these HDL-associated enzymes may contribute to the anti-inflammatory and antioxidative potential of HDL and thereby to the protection conferred by HDL against atherothrombosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1991

Butyrate stimulates the secretion of apolipoprotein (apo) A-I and apo B100 by the human hepatoma cell line Hep G2. Induction of apo A-I mRNA with no change of apo B100 mRNA.

Addition of sodium butyrate to the culture medium of the human hepatoma cell line Hep G2 resulted in a time- and dose-dependent increase in the secretion of apolipoprotein A-I (apo A-I) and apolipoprotein B100 (apo B100). After a 24 h preincubation period, a 2.4- and 2.2-fold increase in the secretion of apo A-I and apo B100 respectively was obtained during the next 24 h in the presence of 2 mM-sodium butyrate. Secretion of albumin, fibrinogen or [35S]methionine-labelled newly synthesized proteins was unaffected or only marginally affected, indicating that the effect of butyrate on apo A-I and apo B100 is not part of a general effect on protein synthesis and secretion. In structure-function studies, butyrate was found to be the most potent inducer among various straight-chain carboxylic acids. Hydroxylated, aminated and otherwise modified butyrate derivatives were inactive. The enhanced accumulation of apo A-I and apo B100 in the culture medium could not be explained by changes in the uptake and degradation of the synthesized apolipoproteins or by alterations in the secretion of possible intracellular pools. In addition, [35S]methionine incorporation studies indicated that synthesis and/or secretion of newly synthesized apo A-I and apo B100 is enhanced in the presence of butyrate. The apo A-I mRNA level was increased 2.3-fold upon treatment with 2 mM-butyrate for 48 h, suggesting regulation at (post-)transcriptional level. In contrast, no change in the level of apo B100 mRNA in butyrate-treated cells was observed, indicating regulation at translational or co- or post-translational level. We propose that the effect of butyrate on the secretion of apo A-I and apo B100 by Hep G2 results from two different regulatory mechanisms.

Albumins↗
PubMed1990

Neonatal apo A-I, apo B, and apo(a) levels in dried blood spots in an Australian population.

We measured neonatal apo A-I and apo B by ELISA, and apo(a) by RIA, in capillary blood spotted onto filter paper in samples also used for routine neonatal screening in 1032 consecutively born babies. In the 2- to 5-d-old babies with birth weights greater than or equal to 2.0 kg (n = 919), mean +/- SD levels of apo A-I and B were 0.48 +/- 0.19 g/L and 0.24 +/- 0.14 g/L of whole blood, respectively. The apo A-I levels were affected by birth weight (negatively) and by age at sampling (positively). The apo B levels were affected positively by both variables, and girls had higher levels than boys (p less than 0.01). These variables accounted for 3.5 and 6.2% of apo A-I and apo B variability, respectively (p less than 0.001). The apo(a) levels (mean +/- SD, 20 +/- 23 U/L; median, 14 U/L, n = 1032) were unaffected by these factors. After adjustment for these variables, apo A-I levels were nearly normally distributed, whereas those of apo B were still positively skewed. The apo(a) distribution was strongly positively skewed and 1.2% of babies had levels above the equivalent of 25 mg/dL of lipoprotein(a) in serum. Our study shows that blood spots can be used to estimate apo A-I, apo B, and apo(a) levels in neonates, and establishes normal ranges. The results suggest that the apo(a) gene is expressed during the 1st postnatal week and that levels are independent of birth weight and apo A-I and B concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1996

Co-regulation of apo A-I, apo C-III and apo A-IV gene expression in human intestinal biopsies.

The apo A-I gene is expressed in the liver and small intestine. In order to study the role of human intestinal transcription of the apo A-I gene in determining plasma high-density lipoprotein, (HDL)-cholesterol and apo lipoprotein (apo) A-I concentrations, the authors measured the relative mRNA levels of apo A-I in human intestinal biopsies. Biopsies were taken from 50 fasting subjects (25 males and 25 females). At the same time blood was taken for lipid and lipoprotein analysis. Plasma HDL-cholesterol correlated linearly with plasma apo A-I protein. No correlation could be demonstrated between intestinal apo A-I mRNA and plasma apo A-I or HDL-cholesterol levels. The apo A-I gene resides in an apolipoprotein cluster with the apo C-III and apo A-IV genes. To assess whether there is a coordinated expression of this locus, Northern blot analysis of intestinal RNA was performed. The authors have demonstrated that under fasting conditions mRNA levels of apo A-I, C-III and A-IV are co-regulated in the intestine.

Adult↗
PubMed1995

Screening for naturally occurring apolipoprotein A-I variants: apo A-I(delta K107) is associated with low HDL-cholesterol levels in men but not in women.

Isoelectric focussing (IEF) in carrier ampholyte-generated pH gradients and hybrid isoelectric focussing (HIEF) in immobilized pH gradients under nondenaturing conditions were used in parallel to screen 5,500 plasma samples for naturally occurring variants of apolipoprotein A-I (apo A-I). The following defects were identified in four unrelated subjects heterozygous for apo A-I variants: apo A-I(delta K107)(2 x), apo A-I(K107M)(1 x), and apo A-I(E41R)(1 x). The later variant is a novel finding. Family studies did not reveal any association of apo A-I(K107M) and apo A-I(E41R) with dyslipidemia, but identified several heterozygotes for apo A-I(delta K107) who had low levels of high density lipoprotein (HDL)-cholesterol. Therefore, and since the apo A-I(delta K107) is the most frequent apo A-I variant in Germany (1: 5,000) we evaluated our data and that reported from 11 families with 32 heterozygous carriers and 30 unaffected controls. This analysis revealed that apo A-I(delta K107) is associated with lower HDL-cholesterol (-30%) and higher triglycerides (+48%) in men but not in women as compared with unaffected family members as well as with controls from the Prospective Cardiovascular Münster (PROCAM) study. Moreover, 11 of 15 male apo A-I(delta K107) heterozygotes but only 2 of 17 female apo A-I(delta K107) heterozygotes had HDL-cholesterol levels below the 20th percentile of sex-matched controls from the PROCAM study. We conclude that heterozygosity for apo A-I(delta K107) decreases HDL-cholesterol and increases triglycerides in men but not in women.

Apolipoprotein A-I↗
PubMed1998

A novel homozygous missense mutation in the apo A-I gene with apo A-I deficiency.

We analyzed the genetic defect in a 67-year-old Japanese male patient with apolipoprotein (apo) A-I and high density lipoprotein (HDL) deficiencies, corneal opacities, and coronary artery disease. The plasma concentrations of apoA-I and HDL cholesterol were 2.9 to 7.3 mg/dL and 0.08 to 0.19 mmol/L, respectively. The lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate were <40% of normal control values. LCAT mass was 550% of normal control. Sequence analysis of polymerase chain reaction-amplified DNA of the proband's apoA-I gene showed a homozygous T-to-A transition resulting in the substitution of Val 156 with Glu (apoA-I Oita). Direct sequencing of samples obtained from other family members showed that the brother was homozygous, whereas the son was a heterozygous carrier of apoA-I Oita. The heterozygote for apo A-I Oita showed nearly 60% of normal apoA-I and normal HDL cholesterol levels. In vivo turnover studies in rabbits demonstrated that the variant apoA-I was rapidly cleared from plasma compared with normal human apoA-I. Our data suggest that the Val156Glu substitution is associated with apoA-I and HDL deficiency, partial LCAT deficiency, and corneal opacities and that Val156 of apoA-I may play an important role in apoA-I function.

Aged↗
PubMed2004

Inhibition of cholesteryl ester transfer protein increases serum apolipoprotein (apo) A-I levels by increasing the synthesis of apo A-I in rabbits.

BACKGROUND: Inhibition of cholesteryl ester transfer protein (CETP) is an effective way to increase HDL levels in animals and humans. The effects of a CETP inhibitor, JTT-705, on the in vivo kinetics of apolipoprotein (apo) A-I and apo A-I gene expression in the liver and intestine were investigated. METHODS: Japanese White rabbits were randomly fed normal rabbit chow LRC-4 (n=10, control) or a food admixture of LRC-4 and 0.75% JTT-705 (n=10, treated) for 7 months. An in vivo kinetics study of apo A-I was performed by injecting rabbit 125I-apo A-I, and apo A-I mRNA levels were quantified by RT-PCR. RESULTS: JTT-705 significantly inhibited CETP activities, increased serum levels of HDL-cholesterol (C), HDL2-C, HDL-phospholipid, and apo A-I, and decreased HDL-triglyceride levels. The synthetic rate of apo A-I was higher in the treated rabbits than in control rabbits (13.7 +/- 2.6 versus 9.5 +/- 1.3 mg/kg per day, P < 0.05), while the fractional catabolic rate was similar in the two groups. JTT-705 increased apo A-I mRNA levels in the liver without affecting those in the intestine. CONCLUSION: Inhibition of CETP activity by JTT-705 increases HDL levels by increasing the synthesis of apo A-I, suggesting that it could be a promising therapeutic approach for atherosclerosis.

Amides↗
PubMed2004

Hyperexpression of N-acetylglucosaminyltransferase-III in liver tissues of transgenic mice causes fatty body and obesity through severe accumulation of Apo A-I and Apo B.

N-Acetylglucosaminyltransferase (GnT)-III catalyzes the attachment of an N-acetylglucosamine (GlcNAc) residue to mannose in beta(1-4) configuration in the region of N-glycans and forms a bisecting GlcNAc. To investigate the pathophysiological role of dysregulated glycosylation mediated by aberrantly expressed GnT-III, we generated transgenic mice hyperexpressing the human GnT-III in the liver by introducing human GnT-III cDNA under the control of mouse albumin enhancer/promoter. Total five transgenic founder mice (pGnTSVTpA-10, -14, -20, -25, and -51) expressed the human GnT-III in their livers and were characterized by molecular genetic means. The copy number of transgene integrated into the genome of these mice ranged between 1 and 3 copies per haploid genome. Northern and Western blot analyses showed that the transgene is specifically expressed in the liver but not in any other tissues tested. The triglyceride level in GnT-III transgenic mice was significantly decreased, however, no significant differences in the levels of glucose, cholesterol, or albumin were observed between transgenic and nontransgenic mice. Although glutamate oxaloacetic transaminase and glutamic pyruvic transaminase activities of transgenic mice were also higher than those of nontransgenic mice, no differences in total bililubin and total protein were observed between the two animal lines. Large amounts of apolipoprotein (Apo) A-I and Apo B were specifically detected in the intracellular liver of transgenic mice. The accumulation of Apo A-I in hepatocytes may be due to aberrant glycosylation, since glycosylated Apo A-I was not observed in transgenic mice. However, the accumulated Apo B was severely glycosylated. Therefore, it is suggested that highly expressed transgenic GnT-III allowed unknown target proteins to be glycosylated in large amounts, and the resulting target protein(s) disrupted in assembly formation of Apo A-I in the hepatocytes and cause a decrease in the release of lipoproteins and accumulations of Apo A-I and Apo B in the liver. The transgenic mice showed aberrant glycosylation by GnT-III, resulting in numerous lipid droplets in liver tissues and the obesity. These mice showed microvesicular fatty changes with abnormal lipid accumulation in the hepatocytes. Our study provides the basis for future analysis of the role of glycosylation in hepatic pathogenesis. In the transgenic mice, Apo A-I and Apo B were significantly increased compared with levels in nontransgenic liver tissues.

Alanine Transaminase↗
PubMed1991

Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia.

Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility.

Apolipoprotein A-I↗
PubMed1991

[Studies on serum levels of normal and cholesterol-fed Beijing duck apo A-I and apo B].

Rabbit anti-Beijing duck apo A-I and apo B antisera were prepared by immunizing New Zealand rabbits with duck apo A-I and LDL, respectively. Rocket immunoelectrophoresis and radial immunodiffusion were used to determine the serum levels of apo A-I and apo B of 55 normal Beijing ducks and 8 cholesterol-fed Beijing ducks. Normal ducks contained about 145 mg apo A-I and 73 mg apo B per 100 ml serum; cholesterol-fed ducks contained about 167 mg apo A-I and 75 mg apo B per 100 ml serum.

Animals↗
PubMed1994

Lipoprotein analysis in transgenic mice expressing human apolipoprotein (apo) A-I and apo C III: use of micromethods in analysis of lipoprotein system in mice.

Transgenic animal technology has added a new dimension to the study of lipoprotein physiology. The unique advantage of the technology is that the exact physiological role (s) of a gene and the corresponding protein whose function (s) has been undefined may be revealed in vivo by the expression or inactivation of the expression of the gene. Although mice are most frequently used transgenic animals, the lipoprotein system has not been studies extensively. This report primarily focuses on practical applications of the existing laboratory methods to transgenic mice expressing human apoproteins. Described below is the summary of the results obtained from transgenic mice expressing human apo A-I and apo C III. In one line of transgenic mice expressing human apo A-I, the total plasma apo A-I level (mouse plus human) was higher than that in control (mean +/- SEM, 381 +/- 18 vs. 153 +/- 7 mg/dl, n = 6, respectively, p = 0.0001) with 64% increase in the HDL cholesterol (HDL-C) level (90 +/- 3 vs. 55 +/- 5 mg/dl, p = 0.0001). High fat feeding further increased the apo A-I and HDL-C levels. One line of apo C III transgenic mice with approximately 100 copies of human apo C III gene were severely hypertriglyceridemic compared to negative littermates (mean +/- SEM; 959 +/- 217 vs. 49 +/- 6 mg/dl). In a second line, animals with one to two copies of the human apo C III gene manifested mild hypertriglyceridemia. These experiments revealed for the first time in vivo that overexpression of apo A-I and C III could lead respectively to hyperalphalipoproteinemia and hypertriglyceridemia and may suggest possible etiology for these disorders in human.

Animals↗
PubMed1994

[Thrombotic thrombocytopenic purpura (TTP) with a low level of apolipoprotein A-I (Apo A-I) which responded to combination of vincristine and beraprost].

A 51-year-old man was admitted to the psychiatric ward because of increasing confusion and irrational behavior. He was later transferred to our department due to anemia and thrombocytopenia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made based on the presence of thrombocytopenic purpura, microangiopathic hemolytic anemia, neurological symptoms and fever. Corticosteroids, plasma exchange (PE), dextrans, dipyridamole and vincristine (VCR) were given without satisfactory response. Beraprost sodium was prescribed followed by a dramatic improvement and complete remission. A number of reports indicated that prostacyclin metabolism was involved in the pathogenesis of TTP. Recently Apo A-I was identified to be a prostacyclin-stabilizing factor, which was initially low in this patient. If patients do not respond to either PE or VCR, consideration should be given to treatment with beraprost, especially when the level of Apo A-I is low.

Apolipoprotein A-I↗
PubMed1998

Apo A-I and apo E concentrations in cerebrospinal fluids of patients with acute meningitis.

It has been demonstrated that apolipoproteins found in cerebrospinal fluid (CSF) play an important role in lipid metabolism in the central nervous system (CNS). Previously we reported that CSF apo A-I levels increased with the severity of neurological damage in poliovirus-infected macaques. In the present study, apo A-I was quantitatively analysed in CSF from patients with or without neurological diseases. In controls, CSF apo A-I level was significantly higher in males; 3.83 (0.40) mg/L, mean (SEM) (n = 19) compared with females, 2.42 (0.26) mg/L (n = 23, P < 0.05). CSF apo A-I concentrations in patients with acute meningitis increased at the active stage, 7.74 (1.78) mg/L (n = 10), but returned to basal concentrations at the convalescent stage 2.72 (0.38) mg/L (n = 10), while the CSF apo A-I level in patients with other neurological diseases remained in the same range as in controls. By contrast, CSF apo E was consistently elevated at either stage of acute meningitis. Furthermore, it was found that the levels of CSF apo A-I, but not of apo E, correlated positively with CSF albumin concentrations. These findings suggest that the CSF apo A-I and apo E have different origins and may play different roles in the lipoprotein metabolism in CNS.

Acute Disease↗
PubMed1996

Compound heterozygosity for a structural apolipoprotein A-I variant, apo A-I(L141R)Pisa, and an apolipoprotein A-I null allele in patients with absence of HDL cholesterol, corneal opacifications, and coronary heart disease.

BACKGROUND: The concentration of HDL cholesterol is inversely correlated with the risk of coronary heart disease (CHD). Some rare mutations in the apolipoprotein (apo) A-I gene are associated with low levels of HDL cholesterol. Their association with cardiovascular risk is controversial. METHODS AND RESULTS: We studied the molecular defects underlying corneal opacities and absence of HDL cholesterol in three brothers and a sister. In a family study, the importance of these defects for lipid metabolism and manifestation of coronary heart disease was investigated. The frequency of these apo A-I defects was assessed by genotype and phenotype analysis of 477 DNA- and plasma samples, respectively, from the population. The four patients were compound heterozygotes for a null allele and a missense mutation in the apo A-I gene that leads to a leucine-->arginine substitution at residue 141 [apo A-I(L141R)Pisa]. Heterozygotes for either the null allele or the structural variant had half-normal concentrations of HDL cholesterol and apo A-I compared with unaffected family members. Apo A-I(L141R)Pisa was detected in one more unrelated subject. Coronary angiography of the four compound heterozygotes revealed the presence of CHD in all male patients, whose ages ranged between 45 and 52 years. They presented with additional risk factors, including elevated LDL cholesterol levels, obesity, and arterial hypertension. Despite complete HDL deficiency and hypercholesterolemia, CHD was absent in the 51-year-old premenopausal sister. CONCLUSIONS: Apo A-I deficiency may lead to premature atherosclerosis if present in conjunction with additional cardiovascular risk factors.

Adolescent↗