Serum Levels Of Apo Research Articles

Decreased Serum Lipoprotein Levels as a Guide for Clinical Severity in Patients with Idiopathic Dilated Cardiomyopathy

Hyperlipidemia is a cardiovascular risk factor. In patients with idiopathic dilated cardiomyopathy (IDC), prognostic roles of endogenous lipoproteins are not fully clarified. It has been known that there is a direct relationship between the levels of cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and deteriorating functional classes of heart failure and mortality. The present study compared the levels of circulating TNF-alpha, IL-6, lipoproteins, and apolipoproteins in patients with stable IDC (n = 28) with those of patients with unstable IDC (n = 26) and controls (n = 24). Mean serum total cholesterol (TC) was significantly lower in stable IDC patients than controls (p < 0.05). In unstable IDC patients, mean serum TC was also lower than controls but not statistically significant. The IDC patients had significantly higher concentrations of IL-6 and TNF-alpha than the controls (p < 0.01). Serum IL-6 and Apo AI levels were significantly different between stable and unstable IDC patients (p = 0.021 and p = 0.012, respectively). Increased levels of IL-6 were associated with decreased levels of TC (r = -0.266, p = 0.019), LDL-C (r = -0.376, p = 0.001) and apolipoprotein AI (apo AI) (r = -0.495, p < 0.001) in all IDC patients. TNF-alpha was also inversely related to apo AI (r = -0.455, p < 0.001) and LDL-C (r = -0.364, p = 0.001) in all patients. Thus, elevated serum levels of cytokines in patients with IDC are associated with decreased lipoprotein concentrations, which may indicate impaired prognosis.

Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lp(a) levels according to thyroid function status

Altered lipid profile is a well-known manifestation of thyroid dysfunction. Recently, serum Lp(a) and C-reactive protein (CRP) have emerged as new cardiovascular risk factors, but studies on changes of these markers with respect to thyroid function status have produced variable results. To better understand the effects of thyroid dysfunction on the development of atherosclerosis, we investigated plasma CRP and lipid profiles such as apoA1, apoB, and Lp(a) in cases with differing severities of thyroid dysfunction. Fifty four patients with hyperthyroidism, 35 patients with subclinical hyperthyroidism, 33 patients with overt hypothyroidism, 190 patients with subclinical hypothyroidism and 100 age- and sex-matched healthy control subjects were evaluated. Serum high sensitivity (hs)-CRP and Lp(a) were measured by immunonephelometry. No significant differences were found in serum hs-CRP, Lp(a), HDL-C or ApoA1 in different thyroid function groups. Serum total cholesterol and LDL-C levels were significantly lower in cases of hyperthyroidism than in cases of overt hypothyroidism, subclinical hypothyroidism or subclinical hyperthyroidism, or in healthy control subjects (p <0.01). Serum triglyceride levels were higher in overt hypothyroidism than in hyperthyroidism or healthy controls (p <0.05). Serum apoB levels were significantly lower in hyperthyroidism than in overt hypothyroidism, subclinical hypothyroidism or in healthy control subjects (p <0.01). These differences were consistently significant after adjustment for age and BMI. Serum CRP and Lp(a) levels, risk factors for atherosclerosis, were not found to be significantly affected by the degree of thyroid dysfunction. Increased risk of atherosclerosis in hypothyroidism does not appear to be associated with non-traditional cardiovascular risk factors, such as serum CRP, Lp(a) or apoA1 levels.

Prognostic value of lipoproteins and their relation to inflammatory markers among patients with coronary artery disease

Background Lipoproteins and their subfractions are associated with the incidence of atherosclerotic diseases. In patients with coronary artery disease (CAD), low serum concentrations of high density lipoprotein (HDL) and high low-density lipoproteins (LDL) are correlated to myocardial infarction and cardiovascular death. There is growing evidence indicating that those lipoprotein factors are related to the inflammatory process in atherogenesis. Methods We investigated in a median follow up of 3.9 years the association of HDL, apolipoprotein A-I (apoA-I), LDL, apolipoprotein B (apoB), and triglycerides with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) and their relation to markers of inflammation in 1298 patients with angiographically documented CAD. Results In univariate analysis, serum concentrations of apoA-I were significantly and inversely related to the combined endpoint, whereas serum concentrations of LDL, apoB, and triglycerides were not. HDL was not significantly related to the endpoint in univariate analyses ( p=0.057). Multivariate analyses showed that only apoA-I is an independent predictor. ApoA-I (and HDL) was significantly related to markers of inflammation. Conclusion Serum apoA-I levels were an independent predictor for fatal and non-fatal cardiovascular events in patients with CAD. This may be related to its anti-inflammatory effect.

The influence of serum apolipoprotein E concentration and polymorphism on serum lipid parameters in hemodialysis patients

Background: Apolipoprotein E (ApoE) polymorphism has been shown to influence serum lipid parameters and ApoE levels in both healthy subjects and hemodialysis (HD) patients. Conversely, ApoE concentration significantly affects serum lipid levels in the general population, independently of ApoE polymorphism, by modulating lipoprotein production, lipolytic conversion, and receptor-mediated clearance. Therefore, studying the effect of ApoE polymorphism on serum lipid levels without taking into account ApoE levels could lead to confounding results. However, such a combined study has not been performed in HD patients to date. Methods: Three hundred one patients without diabetes on long-term maintenance HD therapy and 200 matched healthy subjects were studied. Determination of levels of fasting serum ApoE and other lipid parameters, as well as common ApoE genotypes, was performed in all subjects. Results: HD patients had a significantly lower prevalence of the ɛ4 allele and greater levels of ApoE compared with the control population. ApoE2 allele carriers had significantly lower levels of ApoB and serum total, low-density lipoprotein, and non-high-density lipoprotein cholesterol, as well as increased ApoE levels. When ApoE levels were included in analysis, ApoE levels themselves were proven to be important determinants of serum lipid levels, whereas the effect of ApoE polymorphism became more pronounced. The combination of these 2 factors explains a much greater percentage of the variation in the studied parameters than each factor alone. Conclusion: For the first time, our study provides data to support that ApoE concentration in combination with the ApoE polymorphism significantly influences serum lipid parameters in HD patients.

PXR and the regulation of apoA1 and HDL-cholesterol in rodents

Orphan nuclear receptors (ONRs) have been implicated in the regulation of lipids. Several clinical studies conducted either prospectively or epidemiologically have pointed to a link between the regulation of hepatic CYP enzymes and HDL-cholesterol (HDL-C) and/or apolipoprotein A1 (apoA1). The treatment of rats with a series of imidazole inducers of CYP3A yielded correlations between in vitro CYP3A activity measured as erythromycin demethylase activity and plasma HDL-C and hepatic apoA1 mRNA. Similarly, a correlation was established between in vivo CYP3A activity, measured as ethosuximide clearance, and plasma HDL-C and hepatic apoA1 mRNA. The treatment of wild-type (WT) mice with PXR agonists elicited increases in serum HDL-C and serum apoA1 levels. On the other hand, the treatment of PXR-knockout mice (PXR-KOs) with the same PXR agonists failed to elicit increases in either serum HDL-C or serum apoA1 levels. Superposition of the structures of three imidazoles known to be active CYP3A inducers in rats with the human PXR pharmacophore demonstrated a partial fit and predicted EC 50 values typical of weak-moderate hPXR inducers in humans. These imidazoles have been shown to increase apoA1 and HDL-C in rats and mice. Taken together, these data suggest that PXR plays an important role in the regulation of apoA1 and HDL-C in rodents.

W09.233 Apolipoprotein E polymorphism in Northwestern Greece: Frequency and effect on lipid parameters

Astract. Apolipoprotein (apo) E gene polymorphism and its effect on serum lipid parameters were examined in a Greek population originating from northwestern Greece (n = 555). The allele frequencies were e2: 6.3%, e3: 80.7%, and e4: 13.0%. The e4 allele frequency was higher in our population than was previously reported in individuals from other parts of Greece. ApoE polymorphism was associated with significant differences in serum lipid, and lipoprotein levels. Particularly, individuals with the e2 allele had higher serum triglyceride and apoE levels and lower levels of total cholesterol, low-density lipoprotein cholesterol, and apoB, compared to those with the alleles e3 and e4. However, the impact of the e4 allele on lipid parameters seen in other populations was not observed in our population. Furthermore, the combination of apoE polymorphism and serum apoE concentration explained a larger percentage of serum lipid variability than the polymorphism alone. In conclusion, the results of our study suggest that ethnic differences, as well as alterations of serum apoE levels, significantly modify the relationship between apoE gene polymorphism and serum lipid variability. (received 1 March 2004; accepted 1 May 2004)

Associations between serum high-density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA1 gene in Japanese school-aged children

ATP-binding cassette transporter A1 (ABCA1) plays an important role in apolipoprotein AI (apoAI)-mediated cholesterol efflux from peripheral cells. The mild changes in ABCA1 activity due to genomic variation might be associated with interindividual variations in serum high-density lipoprotein cholesterol (HDL-C) and apoAI levels, or primary hypoalphalipoproteinemia in the general population. In the present study, we analyzed the relationships between 5 single nucleotide polymorphisms (SNPs) and 2 insertion/deletion polymorphisms in the 5′ flanking region and 5 missense polymorphisms of the ABCA1 gene and serum lipid levels in healthy school-aged children. We detected significant associations between the K219R and V771M polymorphisms, and HDL-C or apoAI levels. The present data support the proposition that the K219 allele is an anti-atherogenic allele with increased cholesterol efflux activity. Similarly, the M771 allele appears to be anti-atherogenic, although the frequency of the M771 allele is low.

Effects of leptin receptor gene 3'-untranslated region polymorphism on metabolic profiles in young Japanese men.

We investigated the effects of leptin receptor gene 3'-untranslated region (3'-UTR) polymorphism on clinical and metabolic parameters in 221 young Japanese men aged 21 to 28 years. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify a pentanucleotide (CTTTA) insertion in 3'-UTR of the leptin receptor gene. Body mass index, blood pressure, plasma glucose, insulin, leptin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, free fatty acids, uric acid, apolipoprotein A-I (apoA-I), and cholesteryl-ester transfer protein levels were measured. There was only 1 homozygote and 38 heterozygotes for the 3'-UTR insertion allele among the 221 subjects. The insertion allele frequency was 0.090. Plasma HDL-cholesterol and apoA-I levels were significantly lower (p = 0.015 and p = 0.032 by Mann-Whitney U test, respectively) in homozygous or heterozygous carriers of the insertion allele than in subjects homozygous for the normal allele. There were no differences in other parameters measured. Furthermore, when the subjects were divided into three groups according to HDL-cholesterol level, the percentage of insertion allele-positive subjects was significantly lower in the highest HDL-cholesterol group (chi(2) = 8.42, p = 0.015). These findings suggest that serum HDL-cholesterol and apoA-I levels are influenced by the leptin receptor gene 3'-UTR polymorphism in young Japanese men.

Human apoB contributes to increased serum total apo(a) level in LPA transgenic mice

BackgroundThe Lp(a) lipoprotein (Lp(a)) consists of the polymorphic glycoprotein apolipoprotein(a) (apo(a)), which is attached by a disulfide bond to apolipoprotein B (apoB). Apo(a), which has high homology with plasminogen, is present only in primates and hedgehogs. However, transgenic mice and rabbits with high serum apo(a) levels exist. Liver is the main site for apo(a) synthesis, but the site of removal is uncertain. To examine differences between transgenic mice expressing the LPA gene and mice capable of forming Lp(a) particles, LPA-YAC transgenic mice and hAPOB transgenic mice were crossed and their offspring examined.ResultsComparison of LPA-YAC with LPA-YAC/hAPOB transgenic mice showed that LPA-YAC/hAPOB transgenic mice have higher serum total apo(a) and total cholesterol level than mice lacking the hAPOB gene. However, hepatic apo(a) mRNA level was higher in LPA-YAC transgenic mice than in LPA-YAC/hAPOB transgenic mice. Feeding of a high-cholesterol/high-fat diet to male LPA-YAC transgenic mice with or without the hAPOB gene resulted in reduced serum total apo(a) and hepatic apo(a) mRNA level.ConclusionIn conclusion, the higher serum total apo(a) level in LPA-YAC/hAPOB transgenic mice than in LPA-YAC transgenic mice is not caused by increased apo(a) synthesis. Lower hepatic apo(a) mRNA level in LPA-YAC/hAPOB than in LPA-YAC transgenic mice may suggest that the increase in total apo(a) level is a result of apo(a) accumulation in serum. Furthermore, observed higher serum total cholesterol level in LPA-YAC/hAPOB transgenic mice than either in wild type or LPA-YAC transgenic mice may further suggest that human APOB transgenicity is a factor that contributes to increased serum total apo(a) and cholesterol levels. Our results on reduced serum total apo(a) and hepatic apo(a) mRNA levels in HCHF fed male LPA-YAC transgenic mice confirm earlier findings in females, and show that there are no sex difference in mechanisms for lowering apo(a) level in response to HCHF feeding.

Serum lipids, lipoproteins and apolipoproteins levels in patients with nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a form of liver disease that is histologically indistinguishable from alcoholic hepatitis but occurs in persons who do not consume alcohol in excess. The objectives of this study are to measure serum levels of lipids, lipoproteins and apolipoproteins (apo AI, apo B), lipoprotein (a) [Lp (a)] in patients with nonalcoholic steatohepatitis (NASH), and to investigate the relationship with liver histology. The scope of this study is composed of 36 patients (27 males, 9 females) with NASH, diagnosed by biochemical liver function tests, sonographic examination of liver and liver biopsy and 32 healthy adults as a control group (22 males, 10 females). Serum lipids, lipoproteins and apo AI, apo B, and Lp (a) measurements were taken in the study group and controls, and a correlation with histopathologic findings was searched for. Serum mean levels (+/- SD as mg/dl) of total cholesterol (201.05 +/- 34.48), triglyceride (225.94 +/- 156.50), and LDL-cholesterol (111.77 +/- 19.85) in patients with NASH were significantly higher than those of the control group (170.68 +/- 31.06; 138.81 +/- 49.96; 100.68 +/- 17.98; respectively) and serum HDL-cholesterol level (41.22 +/- 2.47) was less than that of the control group (45.06 +/- 8.32) (P = 0.017). The serum mean level of apo AI (151.54 +/- 30.90) in the study group was lower than that of the controls (160.62 +/- 22.11), but the difference was not significant (P = 0.17). However, the serum apo AI level in patients with liver fibrosis (140.62 +/- 35.62) was significantly lower than that of patients without liver fibrosis (164.57 +/- 25.47) (P = 0.01). The serum mean level of apo B (89.80 +/- 20.62) in the patients was significantly higher than the control group (73.25 +/- 25.39) (P = 0.004), but not correlate with liver histopathology. The serum Lp (a) levels in both the patients (13.09 +/- 9.61) and the controls (12.01 +/- 7.50) were not different (P = 0.61). Hypertriglyceridemia (above 220 mg/dL) had a positive correlation with steatosis of the liver (r = 0.333, P = 0.04) and a negative correlation with liver fibrosis (r = -0.438, P = 0.008). There was a significant negative correlation between apo AI and steatosis (r = -0.360, P = 0.03), inflammation (r = -0.364, P = 0.03) and fibrosis of liver (r = -0.418, P = 0.01). A positive correlation of serum LDL-cholesterol (r = 0.507, P = 0.002) and Lp(a) (r = 0.394, P = 0.01) concentrations with liver fibrosis was also noted. Abnormalities of lipid metabolism such as the increase of serum triglyceride, cholesterol and LDL-cholesterol level and decrease of HDL-cholesterol may be the contributing factors in the development of NASH. The decrease in apo AI and the increase in LDL and Lp (a) in patients were correlated with liver fibrosis. Apo AI may be a serum marker for liver fibrosis in patients with NASH.

Low serum apolipoprotein AI levels in amyloidosis related to familial Mediterranean fever

Amyloidosis (A) related to familial Mediterranean fever (FMF) causes serious morbidity and mortality in children. Our study evaluates serum levels of apolipoprotein (Apo) AI, AII, B, and E and Apo AII/AI ratios as a non-invasive diagnostic tool for amyloidosis in children with FMF and FMF-A. Results were compared with those of patients with childhood nephrotic syndrome (NS) and healthy children (controls). Significantly lower serum levels of Apo AI (90.20+/-28.30 mg/dl) were documented in patients with FMF-A than in all other groups (FMF 126.89+/-51.07 mg/dl, NS 140.38+/-33.73 mg/dl, and controls 134.67+/-12.73 mg/dl) ( P<0.01). Diagnostic sensitivity, specificity, and predictive value for this test were 85%, 80%, and 85%, respectively. Apo AII/AI ratio results were essentially equal in all groups ( P>0.05). It is concluded that a decreased Apo AI serum level, but not Apo AII/AI ratio, is a useful, non-invasive test for the early diagnosis of FMF-A in children.

Effect of Ramadan Fasting on Clinical and Biochemical Parameters in Healthy Adults

Effect of Ramadan Fasting on Clinical and Biochemical Parameters in Healthy Adults

Dietary Fats Differentially Modulate the Expression of Lecithin:Cholesterol Acyltransferase, Apoprotein-A1 and Scavenger Receptor B1 in Rats

In the present study the effects of dietary fat with defined fatty acids on lecithin:cholesterol acyltransferase (LCAT) and apoA-1, the two components of HDL that play a major role in reverse cholesterol transport (RCT), were examined. In addition, the expression of scavenger receptor B1 (SR-B1), the receptor involved in the uptake of HDL core lipids, was also determined under the same conditions in rats fed semisynthetic diets supplemented with triolein (TO), tripalmitin (TP) or menhaden oil (MO). Serum LCAT activity [ micro mol CE/(L.h)] was significantly (P < 0.05) higher in rats fed TO (33 +/- 4) compared with those fed TP (23 +/- 3) or MO (21 +/- 1). The levels of hepatic LCAT mRNA and hepatic SR-B1 receptor protein did not differ between rats fed TP and MO. The triolein diet, on the other hand, increased the induction of hepatic LCAT mRNA and hepatic SR-B1 receptor protein 1.5- to 2-fold. Serum HDL cholesterol concentrations differed among all groups and were 1.30 +/- 0.08, 1.17 +/- 0.10 and 0.91 +/- 0.06 mmol/L for TO-, TP- and MO-fed rats, respectively. Serum apoA-1 levels were significantly higher in TO-fed rats than in the other two groups. The data indicate that TO increases the secretion of HDL and its components (apoA-1 and LCAT), and stimulates the production of hepatic SR-B1 receptor protein. Overall, these results suggest that triolein may promote RCT and thus retard the development of atherosclerosis.

Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis

Hyperlipemia characterizes nephrotic syndrome (NS) and contributes to the progression of the underlying nephropathy. The data in the literature support an implication of apolipoprotein E (apoE) in both hyperlipemia and focal segmental glomerulosclerosis (FSGS), a malignant condition associated with NS. The apoE genotype was determined in 209 nephrotic patients, who were classified according to age and their response to steroids as resistant children (N = 96) and adults (43), and steroid dependent (33) and steroid responder (37) children. A total of 123 presented the histological features of FSGS. In a subgroup of 28 patients, serum and urinary levels of apoE and renal deposits were evaluated by immunofluorescence. The allelic frequencies of the three major haplotypes epsilon2, epsilon3, and epsilon4 were the same in nephrotic patients versus controls, and homozygosity for epsilon3epsilon3 was comparably the most frequent genotype (70 vs. 71%) followed by epsilon3epsilon4, epsilon2epsilon3, epsilon2epsilon4, epsilon4epsilon4. Serum levels of apoE were fivefold higher in NS and in FSGS patients than in controls, with a direct correlation with hypercholesterolemia and proteinuria. ApoE genotypes did not influence serum levels. Urinary levels were 1/10,000 of serum with an increment in nephrotic urines. Finally, immunofluorescence demonstrated the absence of apoE in sclerotic glomeruli, while comparably nephrotic patients with membranous nephropathy had an increased glomerular expression of apoE. ApoE is dysregulated in NS with a marked increment in serum, which is a part of the complex lipid metabolism. Down-regulation of glomerular apoE instead is a peculiarity of FSGS and may contribute to the pathogenesis of the disease. The normal distribution of apoE genotypes in nephrotic patients with FSGS excludes a pathogenetic role of genetic variants.

Hepatic apolipoprotein A-I gene expression in patients with cholesterol gallstones treated with ursodeoxycholic acid

Objective: It has been suggested that apo A-I can inhibit cholesterol crystal nucleation in vitro, and ursodeoxycholic acid (UDCA) is a safe and effective treatment for selected patients with cholesterol gallstones the aim of this study was to investigate the effect of UDCA on the steady-state levels (SSL) of apo A-I mRNA in the liver, as well as serum apo A-I, in patients with cholesterol gallstones.Design: Twenty Mexican patients with symptomatic radiolucent gallstones were randomized and assigned in a double blind fashion to groups that were administered either UDCA (4 mg/kg per day) or placebo for 10 to 15 days before cholecystectomy.Methods: Apo A-I mRNA levels in liver and gallbladder tissues were determined by northern blot and serum levels of apo A-I by turbidimetric method.Results: Apo A-I mRNA levels were higher in nine of the 10 patients who received UDCA and in comparison to those to the placebo group. In the gallbladder apo AI mRNA levels were undetected. Serum levels (mg/dL) of apo A-I were similar in both UDCA and placebo groups after treatment (111.7 ± 29.8 vs 115.6 ± 25.4).Conclusions: The results of this study shown that apo A-I mRNA gene express at the mRNA level in the liver but not in the gallbladder of patients with cholesterol gallstones treated with UDCA.

Are the Effects of Tamoxifen on the Serum Lipid Profile Modified by Apolipoprotein E Phenotypes?

Background: Tamoxifen has favorable effects on the serum lipid profile. It has been suggested that the apolipoprotein (Apo) E phenotype can influence serum lipid parameters; the ApoE allele 4 (ApoE4) is associated with higher total and low-density lipoprotein (LDL) cholesterol levels. The ApoE phenotype also affects lipid responses to diets or treatment with statins. However, the effect of tamoxifen on the lipid profile in different ApoE phenotypes is unknown. Patients and Methods: In the present study, we evaluated the effects of tamoxifen on the serum lipid profile in 11 ApoE4-positive postmenopausal women with breast cancer (phenotypes 3/4 and 4/4) compared with 33 ApoE4-negative women (phenotypes 3/2 and 3/3). Serum lipid parameters [high-density (HDL), LDL and total cholesterol, triglycerides, ApoAI, ApoB and lipoprotein (a)] were measured after an overnight fast before treatment and after 3 and 12 months. ApoE isoforms were determined by isoelectric focusing of delipidated very-low-density lipoproteins (VLDL). Results: During the follow-up period, serum levels of total and LDL cholesterol and ApoB decreased significantly in both groups, but no significant differences were found. Concentrations of serum HDL cholesterol were not significantly different between both groups. However, serum ApoAI levels increased significantly in ApoE4-negative subjects (p = 0.00005), but no significant changes in ApoE4-positive women were observed. Serum triglyceride levels increased by 23.2% (p < 0.05) in ApoE4-positive patients, but they did not change significantly in ApoE4-negative patients. The LDL/HDL cholesterol ratio decreased similarly in the two groups, but the ApoAI/ApoB ratio, which may be a better predictor of cardiovascular events, significantly changed in the ApoE4-negative subjects. Finally, the median level of Lp(a) decreased by 43.4% in the ApoE4-negative patients, whereas it did not change significantly in the ApoE4-positive group. Conclusion: In postmenopausal Greek women with breast cancer, the levels of Lp(a) and triglycerides and the ApoAI/ApoB ratio respond more favorably to tamoxifen treatment in ApoE4-negative than in ApoE4-positive patients.

Coronary artery disease in patients at low risk — apolipoprotein AI as an independent risk factor

Many risk factors for coronary artery disease (CAD) have been established by large epidemiological studies. However, some patients without the major risk factors still develop disease. Preliminary analysis of individuals referred for angiography, who had no major risk factors associated with CAD, indicated that apolipoprotein-AI (apoAI) was significantly lower in patients with positive angiograms. The hypothesis that apoAI was an independent risk factor for CAD in low risk populations was put forth. One thousand and seventy-five consecutive patients underwent angiography, lipid analysis, and completed a risk factor questionnaire. Individuals with total cholesterol<5.2 mmol/l, high density lipoprotein (HDL)-cholesterol>0.9 mmol/l, systolic blood pressure<140 mmHg and diastolic blood pressure<90 mmHg, no diabetes, and no family history of premature CAD in first degree relatives were selected. Fifty-four patients met these selection criteria, 29 having positive evidence of CAD and 25 with no evidence of disease. Multivariate analysis revealed that, after adjusting for age and gender, serum apoAI level was the only variable predictive of CAD. This effect was independent of HDL cholesterol level and fractional esterification rate of HDL (FER HDL). These results point to an important role for apoAI in the atherogenic process, particularly in populations with no major CAD risk factors. Decreased levels of apoAI or LpAI may initiate atherosclerosis in a highly selected group of low risk patients.

Lipoprotein abnormalities in patients with secondary renal amyloidosis.

The prevalance of hyperlipidemia in chronic renal failure (CRF) patients is higher than in general population. Secondary amyloidosis is a common cause of CRF in Turkey. In this study, 25 patients with CRF due to secondary renal amyloidosis (amyloid-CRF), 15 patients with CRF without amyloidosis-CRF and 17 healthy controls were studied for serum lipid parameters. The mean serum lipoprotein (a) [LP(a)] level in the patients with amyloid-CRF was significantly higher than in the controls (p < 0.01). The mean serum apolipoprotein B (Apo B), apolipoprotein E (Apo E) and triglyceride levels in the patients with amyloid-CRF were very significantly higher than in the controls (p < 0.001). The mean serum total cholesterol, low-density lipoprotein (LDL) levels in the patients with amyloid-CRF were higher than in the controls (p < 0.05). The mean serum apo AI levels in the patients with amyloid-CRF was very significantly lower than in the controls (p < 0.001). The mean serum high-density lipoprotein (HDL) in the patients with amyloid-CRF was lower than in the controls (p < 0.05). The mean serum Lp (a), Apo AI, Apo B and Apo E levels in the patients with amyloid-CRF were significantly higher than in the patients with CRF (p < 0.01). The mean serum total cholesterol, trigliserides, LDL and HDL levels in the patients with amyloid-CRF were higher than in the patients with CRF (p < 0.05). There was not any correlation with serum lipid parameters and serum albumin and urine protein levels (p > 0.05). Our study suggests that serum lipid parameters are abnormal and might be the risk factor of atherosclerotic vascular disease and contribute to renal disease progression in the patients with secondary renal amyloidosis and lipid abnormalities were different from CRF with various etiology, without amyloidosis.

Essential role for the (hepatic) LDL receptor in macrophage apolipoprotein E-induced reduction in serum cholesterol levels and atherosclerosis

Apolipoprotein E (apoE) is a high affinity ligand for several receptor systems in the liver, including the low-density lipoprotein (LDL) receptor, and non-LDL receptor sites, like the LDL receptor-related protein (LRP), the putative remnant receptor and/or proteoglycans. Although the liver is the major source of apoE synthesis, apoE is also produced by a wide variety of other cell types, including macrophages. In the present study, the role of the LDL receptor in the removal of lipoprotein remnants, enriched with macrophage-derived apoE from the circulation, was determined using the technique of bone marrow transplantation (BMT). Reconstitution of macrophage apoE production in apoE-deficient mice resulted in a serum apoE concentration of only 2% of the concentration in wild-type C57Bl/6 mice. This low level of apoE nevertheless reduced VLDL and LDL cholesterol 12-fold ( P<0.001) and fourfold ( P<0.001), respectively, thereby reducing serum cholesterol levels and the susceptibility to atherosclerosis. In contrast, reconstitution of macrophage apoE synthesis in mice lacking both apoE and the LDL receptor induced only a twofold ( P<0.001) reduction in VLDL cholesterol and had no significant effect on atherosclerotic lesion development, although serum apoE levels were 93% of the concentration in normal C57Bl/6 mice. In conclusion, a functional (hepatic) LDL receptor is essential for the efficient removal of macrophage apoE-enriched lipoprotein remnants from the circulation and thus for normalization of serum cholesterol levels and protection against atherosclerotic lesion development in apoE-deficient mice.

Apolipoprotein A-I gene expression is upregulated by polychlorinated biphenyls in rat liver

Xenobiotics such as polychlorinated biphenyls (PCB) increase serum cholesterol level (especially high density lipoprotein cholesterol) and apolipoprotein A-I (apo A-I) level in rats. The effect of PCB on serum apo A-I and hepatic apo A-I gene expression and the relationship between apo A-I and drug-metabolizing enzymes in rats were investigated. Serum levels of cholesterol and apo A-I were increased by dietary addition of PCB in a dose-dependent manner (0–500 mg/kg diet). Hepatic apo A-I mRNA level was also elevated by PCB in a similar fashion. Serum level of cholesterol gradually increased during feeding period of PCB (200 mg/kg diet, 105 days) and reached a two-fold higher level in PCB group than in controls. The levels of serum apo A-I and hepatic apo A-I mRNA linearly elevated during feeding period of PCB and were increased 3- or 4-fold, respectively, compared to controls. Although acute administration (16 hr) of PCB, 3-methylcholanthrene, and phenobarbital induced cytochrome P-450 gene expression in the liver, hepatic apo A-I gene expression was not increased by these xenobiotics. These results indicated that the serum levels of cholesterol and apo A-I had positive correlation with hepatic level of apo A-I mRNA in rats fed PCB, and that hepatic apo A-I gene expression was dependent upon intake of PCB but was not directly related to the induction of drug-metabolizing enzymes. This study demonstrated that xenobiotic-induced hyper-alpha-cholesterolemia would be caused by the increased apo A-I gene expression and cholesterol synthesis in the liver, coordinately.