Background: We have previously shown that the effect of a high-density lipoprotein (HDL) genetic risk score depends on whether the phenotype (HDL cholesterol) is high or low relative to its distribution (quantile-dependent expressivity).

Objective: Evidence for quantile-dependent expressivity was sought using a more inclusive genetic measure (quantile-specific heritability, h²) in a larger population (Framingham cohort).

Methods: Quantile regression was used to test whether the offspring-parent (β_OP) and full-sib (β_FS) regression slopes increased with the percentiles of the offspring's HDL distribution in 10,650 parent-offspring pairs and 2130 sibships. Quantile-specific heritability was estimated by 2β_OP/(1 + r_spouse) and [(8β_FSr_spouse + 1)^0.5-1]/(2r_spouse), where r_spouse is the spouse correlation.

Results: HDL cholesterol heritability estimated from β_OP increased significantly (P = 4.2 × 10^-5) from the 10^th (h² ± SE: 0.44 ± 0.03), 25^th (0.45 ± 0.03), 50^th (0.47 ± 0.03), and 75^th (0.56 ± 0.04) to the 90^th percentiles (0.65 ± 0.06) of the offspring's age- and sex-adjusted HDL cholesterol distribution. Heritability estimated from β_FS also increased significantly with the percentiles of the offspring's HDL cholesterol (P = .002), apo A1 (P = .006), HDL2 cholesterol (P = .003), and HDL3 cholesterol distribution (P = .02). Consistent with quantile-dependent expressivity, published pharmacologic and nutritional interventions that raised (eg, statin, fibrates, estrogen replacement therapy, efavirenz, and dietary fat) or lowered HDL cholesterol concentrations (tamoxifen, dietary carbohydrate) correspondingly increased and decreased genetic effects.

Conclusion: HDL cholesterol heritability increased with increasing percentile of the offspring's HDL distribution. Whereas precision medicine is based on the premise that genetic markers identify patients most likely to benefit from drugs and diet, quantile-dependent expressivity postulates that the strong signals from these genetic markers simply trace the heritability increase with increasing plasma HDL concentrations. Thus, quantile-dependent expressivity provides an alternative interpretation to these genotype-specific effects.

Keywords: Apolipoprotein A1; Gene-environment interactions; HDL2; HDL3; Heritability; High-density lipoprotein cholesterol.

UNASSIGNED

Monascin (MS) and ankaflavin (AK) produced by Monascus purpureus NTU 568 were proven to show excellent hypolipidemic effects in our previous studies; however, the mechanism is still unclear.

METHODS

This study used MS, AK, and monacolin K as test substances and performed tests on rats fed high-fat and high-cholesterol diet for 8 weeks. The lipid levels and the related protein levels of the rats were assessed to understand the effects of MS, AK, and monacolin K on lipid metabolism.

RESULTS

MS and AK lowered low-density lipoprotein cholesterol (LDL-C) and preserved high-density lipoprotein cholesterol contents. MS and AK inhibited acetyl-coenzyme A acetyltransferase, microsomal triglyceride transfer protein, and apolipoprotein (apo) B-100 expression, thereby preventing LDL assembly. In addition, enhanced LDL-receptor expression increased the transport of LDL-C to the liver for metabolism. MS and AK also significantly increase apo A1 expression, which facilitates high-density lipoprotein cholesterol formation.

CONCLUSIONS

Monascus-fermented MS and AK can perform blood lipid regulation via the suppression of LDL-C assembly and stimulation of apo A1 expression in liver.

Recently, myoinositol (myo-ins) and folic acid combination has gained an important role for treating Polycystic Ovary Syndrome (PCOS), in addition to combined oral contraceptives (COC). We aimed to examine myo-ins effects on anti-Mullerian hormone (AMH) levels and compare them with those ones obtained administering COC. In this prospective study, 137 PCOS patients, diagnosed according to Rotterdam criteria and admitted to the Reproductive Endocrinology and Infertility Outpatient Clinic at Dokuz Eylul University (Izmir, Turkey), were included. After randomization to COC (n = 60) and myo-ins (n = 77) arms, anthropometric measurements, blood pressure, Modified Ferriman Gallwey scores were calculated. Biochemical and hormonal analysis were performed, and LH/FSH and Apo B/A1 ratios were calculated. Data analysis was carried out in demographically and clinically matched 106 patients (COC = 54; myo-ins = 52). After 3-month treatment, increase in HDL and decreases in LH and LH/FSH ratio were statistically more significant only in COC group when compared with baseline (in both cases p>> 0.05). In myo-ins group, fasting glucose, LDL, DHEAS, total cholesterol, and prolactin levels decreased significantly (for all p < 0.05). Progesterone and AMH levels, ovarian volume, ovarian antral follicle, and total antral follicle counts lessened significantly in both groups (for all p < 0.05). In PCOS treatment, MYO is observed more effective in reductions of total ovarian volume and AMH levels.

<AbstractText>There is a need for novel biomarkers and better understanding of the pathophysiology of diabetic kidney disease.</AbstractText><AbstractText>To investigate associations between plasma metabolites and kidney function in people with type 2 diabetes (T2D).</AbstractText><AbstractText>3,089 samples from individuals with T2D, collected between 1999 and 2015, from five independent Dutch cohort studies were included. Up to 7 years follow-up was available in 1,100 individuals from two of the cohorts.</AbstractText><AbstractText>Plasma metabolites (n=149) were measured by nuclear magnetic resonance spectroscopy. Associations between metabolites and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and eGFR slopes were investigated in each study followed by random effect meta-analysis. Adjustments included traditional cardiovascular risk factors and correction for multiple testing.</AbstractText><AbstractText>In total, 125 metabolites were significantly associated (PFDR= 1.5×10-32 - 0.046; β = -11.98-2.17) with eGFR. Inverse associations with eGFR were demonstrated for branched-chain and aromatic amino acids, glycoprotein acetyls, triglycerides, lipids in VLDL subclasses, and fatty acids (PFDR<0.03). We observed positive associations with cholesterol and phospholipids in HDL and <em>Apo</em> <em>A1</em> (PFDR<0.05). Albeit some metabolites were associated with UACR levels (P<0.05), significance was lost after correction for multiple testing. Tyrosine and HDL-related metabolites were positively associated with eGFR slopes before adjustment for multiple testing (PTyr=0.003; PHDLrelated<0.05), but not after.</AbstractText><AbstractText>This study identified metabolites associated with impaired kidney function in T2D, implying involvement of lipid and amino acid metabolism in the pathogenesis. Whether these processes precede or are consequences of renal impairment needs further investigation.</AbstractText>

Plasmatic lipoproteins were evaluated in a group of 11 professional football-players after a 3-week rest, and one month later, after an intensive training (characterized by a succession of aerobic and anaerobic efforts), for engaging a new competition. At day 0, total cholesterol (TC = 4.4 +/- .04 mmol/l), triglycerides (TG = .6 +/- .04 mmol/l), and LDL-TC (2.54 +/- .18 mmol/l) were significantly decreased versus sex and age matched sedentary subjects (TC = 5.13 +/- .2 mmol/l, P less than .02; TG = .99 +/- . mmol/l, P less than .01; LDL-CT = 3.26 +/- .2 mmol/l, P less than .02). HDL-TC was increased (1.50 +/- .06 vs 1.30 +/- .05 mmol/l, P less than .05). The apoprotein A1 (apoA1) was higher in football-players (1.5 +/- .06 vs 1.16 g/l, P less than .001), while the apoprotein B (apoB) was lower (.6 +/- .03 vs .88 +/- .04 g/l, P less than .001). Even after 3 weeks of rest, the football-players lipoproteins were still identical to aerobic elite-athletes. At day +30, after a daily training involving 2 anaerobic sequences, the maximal aerobic capacity was increased by 21%, without any change in nutritional, plasmatic and hepatic status. Weight was diminished (-0.8 kg, P less than 0.05). TC (4.14 +/- .2 mmol/l), TG less than .64 +/- .08 mmol/l), LDL-TC (3.37 +/- .17 mmol/l), apo B (.64 +/- .05 g/l) were unchanged. HDL-CT fell to controls values while apoA1 increased (1.66 +/- .06 mmol/l, P less than .001). Thus, HDL-CT/apoA1 ratio (indicating the TC content of HDL) was decreased, whereas apoB/apoA1 ratio was unchanged. The decrease of TC content of HDL was not related to dietary change nor to weight decrease. As TG were stable, the lipoprotein lipase activity could not be modified.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE

To investigate the significance of apolipoprotein (Apo)-A1 in urine as a biomarker for early diagnosis and classification of bladder urothelial carcinoma (BUC).

METHODS

Urine samples were divided into four groups: normal control group, benign bladder disease group, low-grade malignant BUC group, and high-grade malignant BUC group. Apo-A1, which showed significantly different expression among the four groups, was selected according to the two-dimensional electrophoresis (2-DE) images of the four groups, and enzyme-linked immunosorbent assay (ELISA) was used to quantify Apo-A1 in the four groups. A receiver operating characteristic (ROC) curve was generated, and the optimal operating points on the ROC curve were found to determine the critical concentrations of Apo-A1 for early diagnosis of BUC and differentiation of low-grade and high-grade malignant BUC. The results were verified clinically, and the specificity and sensitivity were calculated.

RESULTS

The 2-DE images showed that that the level of Apo-A1 increased from the normal control grouP to high-grade malignant BUC group. The ELISA showed that there was no significant difference in Apo-A1 level between the normal control grouP and benign bladder disease group, but the Apo-A1 level was significantly higher in the BUC groups than in the normal control grouP and benign bladder disease grouP (P < 0.01); the high-grade BUC grouP had a significantly higher Apo-A1 level than the low-grade BUC grouP (P < 0.01). The BUC patients and those without BUC could be differentiated with an Apo-A1 concentration of 18.22 ng/ml, while the low-grade and high-grade malignant BUC could be differentiated with an Apo-A1 concentration of 29.86 ng/ml. When used as a biomarker, Apo-A1 had a sensitivity of 91.6% (98/107) and a specificity of 85.7% (42/49) for diagnosis of BUC and had a sensitivity of 83.7% (41/49) and a specificity of 89.7% (52/58) for BUC classification.

CONCLUSIONS

Apo-A1 may be a biomarker for early diagnosis and classification of BUC and shows promise for clinical application.

UNASSIGNED

The biogenesis of high-density lipoprotein (HDL) particles by cholesterol-laden foam cells in atherosclerotic lesions is crucial for the removal of excess cholesterol from the lesions. Impairment in the HDL biogenic process contributes to the progression of atherosclerosis. The aim of this study is to identify novel cellular factors regulating HDL biogenesis.

UNASSIGNED

HDL biogenesis is a process of apolipoprotein (apo)-mediated solubilization of specific plasma membrane (PM) microdomains generated in cholesterol-accumulated cells. We established a new method to isolate PM microdomains interacting with the major HDL protein constituent, apoA-I. Lipidomic and proteomic analyses of an isolated PM microdomain revealed that apoA-I binds to cholesterol-rich and desmocollin 1 (DSC1)-containing microdomains. In this novel apoA-I binding microdomain, DSC1 binds and prevents apoA-I from interacting with another PM microdomain created by adenosine triphosphate-binding cassette transporter A1 (ABCA1) for the formation of HDL. Inhibition of apoA-I-DSC1 binding by silencing DSC1 expression or using DSC1 blocking antibodies increases apoA-I accessibility to ABCA1-created microdomains and thus enhances HDL biogenesis. Importantly, DSC1 is abundantly expressed in macrophages and human atherosclerotic lesions, suggesting that DSC1 may contribute to cholesterol accumulation in atherosclerotic lesions by sequestering apoA-I and impairing HDL biogenesis.

UNASSIGNED

The binding of apoA-I to two functionally opposing PM microdomains, ABCA1 and DSC1 domains, suggests that HDL biogenesis and PM cholesterol levels may be regulated by the relative abundance of the two domains and that novel HDL biogenic therapies may be developed by targeting DSC1.

Leoligin is a natural lignan found in Edelweiss (Leontopodium nivale ssp. alpinum). The aim of this study was to examine its influence on cholesterol efflux and to address the underlying mechanism of action. Leoligin increases apo A1- as well as 1% human plasma-mediated cholesterol efflux in THP-1 macrophages without affecting cell viability as determined by resazurin conversion. Western blot analysis revealed that the protein levels of the cholesterol efflux transporters ABCA1 and ABCG1 were upregulated, whereas the SR-B1 protein level remained unchanged upon treatment with leoligin (10 μM, 24 h). Quantitative reverse transcription PCR further uncovered that leoligin also increased ABCA1 and ABCG1 mRNA levels without affecting the half-life of the two mRNAs in the presence of actinomycin D, a transcription inhibitor. Proteome analysis revealed the modulation of protein expression fingerprint in the presence of leoligin. Taken together, these results suggest that leoligin induces cholesterol efflux in THP-1-derived macrophages by upregulating ABCA1 and ABCG1 expression. This novel activity suggests leoligin as a promising candidate for further studies addressing a possible preventive or therapeutic application in the context of atherosclerosis.

Jerba Island represents an interesting area because four distinct ethnic groups have been cohabiting there until now: Arabs, Berbers, dark-skinned people of sub-Saharan origin and Jews. Religious and cultural differences seem to have constituted an obstacle to their intermixing. Our aim is to provide further information on the genetic structure of the Arab and Berber groups for whom previous data based on haploid markers confirmed their reproductive isolation. Five polymorphic Alu markers (HS 4.69, Sb 19.3, TPA-25, ACE and APO-A1) were analysed in a sample of 43 Arabs and 48 Berbers of Jerba. The genetic relationships among these groups and several populations from North Africa, sub-Saharan Africa and Europe were analysed using genetic distances based on allele frequencies. The results showed a homogeneous distribution of Alu insertions in the two geographically close groups, reflecting ancient relationships between them. This study also revealed that Arabs from Jerba present close genetic distances to other North African populations, whilst Berbers of Jerba occupy an intermediate position among Mediterranean populations.

Levels of sitting among adolescents are high, especially during the school day. The acute cognitive and health consequences associated with prolonged sitting are poorly understood in adolescents. This randomized crossover design study examined the acute effects of a simulated school day with reduced sitting or usual sitting on adolescents' cognitive function and cardiometabolic biomarkers.

Eighteen healthy school aged adolescents were recruited from the community to the study (11 males; 7 females; mean age [SD] = 13.5 ± 0.9 years). Two protocols were developed to simulate an adolescent school day, the amount of time spent sitting was manipulated reflecting: a 'typical' day (65% of the time spent sitting with two sitting bouts sitting >20 min) and a 'reduced sitting' day (adolescents sat for 50% less time with no bouts of sitting >20 mins). The order that participants were exposed to each condition was randomized (via random number generator). Participants were not fully blinded as they could observe the difference between conditions. Energy intake and moderate to vigorous physical activity (MVPA) were standardized for both conditions and monitored for 48 h post-condition for compensatory effects. Cognitive (working memory) and cardiometabolic outcomes (lipids, glucose, insulin, IL-6, apo-A1, apo-B, blood pressure,) were assessed pre and post for both conditions, BMI and body fat were assessed on the morning of the intervention. Data were analyzed using linear mixed models. Standardised effect sizes were calculated.

Compared with the typical school day, the reduced sitting day demonstrated significant positive effects for apoB/apoA-1 ratio (adjusted difference ± SD) -0.02 ± 0.03; P = 0.03; effect size [Cohen's d] = -0.67. Findings for total cholesterol -0.19 ± 0.27; P = 0.28; d = -0.71; HDL cholesterol -0.23 ± 0.50; P = 0.12 d = -0.66; and total cholesterol/HDL ratio 0.25 ± 0.53; P = 0.25; d = 0.51 and for cognition 0.64 ± 0.15; P = 0.15; d = 0.54 were non-significant. There were no compensatory changes in participant energy expenditure or energy intake for 48 h post intervention.

Reducing school day sitting time in adolescents' resulted in significant improvements in apoB/apoA-1 ratio with medium effect sizes for total cholesterol, HDL cholesterol and total cholesterol/HDL ratio. Cognitive function results showed the equivalent of a 6 month improvement in effective mental-attentional capacity.

The trial was registered as a clinical trial with the Australian and New Zealand Clinical Trials Registry ( ACTRN12614001064695 ) on the 3rd of October 2014 - registered retrospectively.

22 nephrectomy specimens of renal allografts in chronic rejection after periods between 3 and 96 months, were studied immunohistologically. Various cell types in the arterial wall were characterized with antibodies specific against different cells of the mononuclear phagocyte system, against smooth muscle cells, and against differentiating lymphoid cells. In addition, the metabolism of lipoproteins was investigated using appropriate antibodies against several apolipoproteins. Subendothelial plaques of foam cells were found to consist of macrophages in foamy transformation. At the stage of intimal fibrosis the smooth muscle cells are more prominent. Lymphatic infiltration consists almost exclusively of T-lymphocytes. Apolipoprotein analysis reveals deposits of Apo A1, A2 and B1, most of them extracellular. According to these results, it is not only immunologic factors that are involved in arterial wall reactions during chronic transplant arteriopathy, but disorders of the lipoprotein metabolism--probably due to endothelial dysfunction--are also playing an important role like in atherosclerosis.

The effect of alcohol feeding on the development of atherosclerosis was investigated in low-density lipoprotein receptor gene-knockout (LDLR-/-) mice. Eight-week-old male mice were pair-fed atherogenic liquid diets containing ethanol at different levels (w/v; group A, 5%; group B, 2.5%; and group C, 0%). Tissue sections of the heart were stained with Oil Red O to examine for fatty lesions in proximal aorta. Results showed that the lesion size of group A was 70% smaller than group C after 6 weeks. By contrast, the lesion size of group B was not significantly different from that of group C. Serum high-density lipoprotein-apolipoprotein A1 (apo A1) A1 in LDLR-/- mice was suppressed by feeding the atherogenic diet, but the decrease was negated by alcohol (both groups A and B). The effectiveness of 5% alcohol to protect against atherosclerosis waned with time, but was still noticeable at 12 weeks, even though serum apo A1 remained high. Serum apolipoprotein E was increased by the high fat diet, but not altered by alcohol in the diet. Our data, therefore, show that: (1) alcohol-feeding impedes early atherosclerosis in LDLR-/- mice (this effect of alcohol is dose-dependent); (2) the protective effect of alcohol is not entirely attributable to an elevated serum high-density lipoprotein-apo A1; and (3) severe impairment of lipoprotein metabolism due to a lack of low-density lipoprotein receptors can eventually overwhelm the protective effect of alcohol against atherosclerosis.

Exposure to nanoparticles has been associated with inflammation-related progression of atherosclerosis. To examine nanoparticle-induced cardiac effects in more detail, we characterized heart gene expression profiles alongside plasma proteins associated with cardiovascular disease in C57BL/6 mice intratracheally instilled with vehicle or 0.162 mg Printex 90 carbon black nanoparticles (CBNPs). Mice were killed 1, 3, and 28 days after the exposure and expression profiles were derived using DNA microarrays. Cardiac gene expression was unperturbed by CBNP exposure in two independent experiments, despite substantive changes in pulmonary and hepatic gene expression. MicroRNAs were not affected. Plasma levels of cell adhesion molecules (sE-selectin, sICAM-1, sVCAM-1) and total PAI-1 were immediately increased up to day 3, whereas Apo-A1 and Apo-E were marginally decreased on day 1. These data suggest that though adverse cardiovascular effects are likely following CBNP exposure, these effects are unlikely to be mediated by major direct effects on cardiac gene expression.

The proteins of the Bcl-2 family play key roles in the regulation of programmed cell death by controlling the integrity of the outer mitochondrial membrane and the initiation of the apoptosis process. We performed extensive molecular dynamics simulations to investigate the conformational flexibility of the Bcl-xL protein in both the apo and holo (with Bad peptide and ABT-737) states. The accelerated molecular dynamics method implemented in Amber 14 was used to produce broader conformational sampling of 200 ns simulations. The pocket mining method based on the variational implicit-solvent model tracks the dynamic evolution of the ligand binding site with a druggability score characterizing the maximal affinity achievable by a drug-like molecule. Major movements were observed around the α3-helical domain and the loop region connecting the α1 and α2 helices, reshaping the ligand interaction in the BH3 binding groove. Starting with the apo crystal structure, which is recognized as "closed" and undruggable, the BH3 groove transitioned between the "open" and "closed" states during equilibrium simulation. Further analysis revealed a small percentage of the trajectory frames (∼10%) with a moderate degree of druggability that mimic the ligand-bound states. The ability to attain and detect by computer simulation the most suitable conformational states for ligand binding in advance of compound synthesis and crystal structure solution is of immense value to the application and success of structure-based drug design.

OBJECTIVE

To determine the effect of raloxifene (RLX) and hormone replacement therapy (HRT) on non-high density lipoprotein cholesterol (non-HDL-C) levels and the apolipoprotein-B/apolipoprotein-A1 (apo-B/apo-A1) concentration ratio, markers of serum atherogenicity, in postmenopausal women.

METHODS

Three hundred and ninety healthy postmenopausal women aged 45-72 years were enrolled in a double-blind, randomized, placebo-controlled, parallel trial at eight outpatient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), 60 or 120 mg/day raloxifene, or placebo for 6 months. Serum concentrations of non-HDL cholesterol and the apo-B/apo-A1 concentration ratio were measured in serum samples obtained at baseline and at 6 months of treatment.

RESULTS

At 6 months, non-HDL-C and apo-B/apo-A1 were significantly reduced by 60 mg/day RLX (10 and 11%, respectively), 120 mg/day RLX (9 and 12%, respectively) and HRT (10 and 12%, respectively), compared with placebo. The effect of all treatments to lower non-HDL-C and apo-B/apo-A1 was greatest in women with hypercholesterolemia (total-C>240 mg/dl) at baseline. Among women with undesirable (>160 mg/dl) non-HDL cholesterol at baseline, RLX and HRT lowered the percentage of these women remaining above this threshold after 6 months (placebo, 89%; 60 mg/day RLX, 61%; 120 mg/day RLX, 74%; HRT, 58%). Similar results were observed for women with high (>190 mg/dl) non-HDL cholesterol at baseline.

CONCLUSIONS

In healthy postmenopausal women, RLX and HRT lower serum non-HDL-C and apo-B/apo-A1, indicators of serum atherogenicity, to a similar extent.

OBJECTIVE

We evaluated the changes in apolipoproteins, glycemic status, and body composition after 3 months using a culturally sensitive diabetes education program, En Balance, in diabetic Hispanics.

METHODS

Thirty-four (9 males, 25 females) Hispanic diabetics participated in the En Balance program over three months. Body composition was determined by dual energy X-ray absorptiometry (DXA), fasting plasma glucose (FPG), A1c, and apolipoproteins (Apo) measured after 3 months participation. Differences were analyzed using paired t testing and relationships between changes in Apo, A1c, total cholesterol, body mass index and body composition by Spearman correlations.

RESULTS

Completion of En Balance resulted in a significant reduction in weight (80.31 +/- 1.97 kg vs 81.25 +/- 17.97 kg, P = .015), FPG (143.21 +/- 57.8 mg/dL vs 166.41 +/- 65.9 mg/dL P = .003), and A1c (7.08 +/- 1.6% vs 7.87 +/- 2.0%, P = < .001). DXA demonstrated reduction in total fat (29.54 +/- 10.0 kg vs 30.24 +/- 11.80 kg, P = < .001) and trunk fat (15.09 +/- 5.6 kg vs 16.87 +/- 5.4 kg, P = .001). High density lipoprotein significantly increased (48.85 +/- 11.4 vs 44.65 +/- 8.8, P = .002) and total serum cholesterol/high density lipoprotein ratio decreased (3.87 +/- .98 vs 4.35 +/- 1.0, P = .001). There were significant correlations at three months between changes in Apo A1 and A2 (r = .559, P < .001), Apo E and total cholesterol (r = .746, P < .001), between A1c and FPG (r = .563, P = .001) and BMI and body weight (r = .732, P < .001).

CONCLUSIONS

The En Balance program improved body composition, A1c, FPG, total cholesterol/HDL ratio and HDL. If these trends can be sustained, En Balance may serve as a unique educational paradigm for improving type 2 diabetes in Hispanics.

Genetic variation of apo A1/C3/A4 is associated with hyperlipidaemia and coronary heart disease. We report the polymerase chain reaction (PCR) conditions for determining three polymorphic sites in the 5'flanking region of apoA1 using DNA prepared from small aliquots of whole blood. These polymorphisms identify six haplotypes that will be of value in genetic studies.

OBJECTIVE

Budd-Chiari syndrome (BCS) is a rare vascular liver disorder caused by thrombosis of the hepatic veins. In some patients, no known thrombophilic factor can be identified. This study aimed to identify novel factors that might play a role in thrombosis in BCS-patients by using a proteomic approach.

METHODS

The abundance of plasma clot-bound proteins was compared between nine BCS-patients and nine controls by using two-dimensional difference gel electrophoresis. The protein with the most significant decrease in patients was identified by mass spectrometry. Plasma levels of this protein were measured and the results were validated in a large cohort of BCS-patients.

RESULTS

A total of 26 protein spots significantly differed (p<0.001). The spot that decreased with the highest statistical significance in patients was identified by mass spectrometry as apolipoprotein A1 (apo A1). The mean level of apo A1 in the plasma of these BCS-patients (0.74 g/L) was also significantly lower than in controls (1.45 g/L, p=0.002). This finding was validated in a large cohort of 101 BCS-patients and 101 controls (0.97 g/L vs. 1.32 g/L, p<0.0001). There was no major correlation between plasma levels of apo A1 and various liver function tests.

CONCLUSIONS

BCS-patients show decreased clot-bound protein abundance and plasma levels of apo A1. Decreased levels of apo A1 may play a role in the etiology of thrombosis in BCS-patients and possibly in other patients with venous thrombosis.

OBJECTIVE

An association of Apolipoprotein B (Apo B) with coronary artery disease (CAD) independent of LDL cholesterol (LDLc) concentrations has been reported in white population. This analysis was taken up to study whether the higher CAD risk in Asian Indians with diabetes could be explained by possible alterations in Apo B and Apolipoprotein A1 (Apo A1) concentrations.

METHODS

The study group consisted of four hundred and forty seven men aged>> or = 25 years, 167 with CAD and 280 with no CAD, classified by coronary angiography. Plasma lipid profile including total cholesterol, LDLc, Apo A1 and Apo B were done. Glucose tolerance was evaluated in all.

RESULTS

Age, BMI, Apo B, and Apo A1 were significantly associated with CAD in a multiple regression analysis. Hyper Apo B was more common than hyper LDLc in CAD (73.6% vs 20.4%, chi2 = 157, P < 0.001). Apo B concentrations were increased in diabetic subjects even in the presence of normal levels of LDLc and in the absence of CAD.

CONCLUSIONS

The study has shown that the apolipoproteins B and A1 provide better information regarding the risk of CAD. Apo B abnormalities exist in large percentages of CAD subjects despite having normal levels of LDLc. Diabetes per se enhances the Apo B concentrations and this could probably be one of the mechanisms of accelerated CAD in diabetes. Hyper Apo B may be an index of CAD risk.

BACKGROUND

There is growing evidence of a link between erectile dysfunction (ED) and coronary artery disease (CAD).

OBJECTIVE

The purpose of this study was to explore the independent determinants of CAD in ED outpatients.

METHODS

This study enrolled 243 patients, ranging in age from 21 to 81 years old, suffering from ED as diagnosed by the International Index of Erectile Function (IIEF) scores. All patients underwent exercise stress tests or thallium-201 single-photon emission computed tomography perfusion imagings. Based on examination results, patients were divided into study (22 patients with a positive finding) and control groups (221 patients with a negative finding).

METHODS

The differences of demographic characteristics, biochemical profiles, pro-inflammatory and inflammatory markers, and echocardiographic characteristics between study and control group were compared.

RESULTS

The age, presence of DM and current smoking status were significant high in the study group. A significant lower high-density lipoprotein (HDL) cholesterol level, a higher percentage of HDL cholesterol level < 40 mg/dL, and a higher apo-lipoprotein B/A1, high sensitive C-reactive protein (hs-CRP) and homocysteine found in the study group. The Framingham cardiac risk scores, the ratio of mitral inflow velocity to early diastolic velocity in the annulus derived by tissue Doppler imaging (E/Et), the ratio of E/Et>> or = 15, the value of carotid intima-media thickness (IMT), and IMT>> or = 1 mm were higher in study group than in the control group. In stepwise multiple logistic regression analysis, a high waist-to-hip ratio (WHR), high IMT, high E/Et, hs-CRP levels, LDL cholesterol>> or = 130 mg/dL, smoking status, and the presence of DM and metabolic syndrome (MS) were independent determinants of CAD in ED patients.

CONCLUSIONS

This study first shows the independent determinants of CAD in ED outpatients. This novel finding may improve the screening of low-risk ED patients for CAD.

OBJECTIVE

We aimed to know the prevalence of classical cardiovascular risk factors, hyperinsulinism, insulin resistance and metabolic syndrome (MS) in a population with coronary heart disease (CHD) as compared with a population without personal or familial history of cardiovascular risk factors.

METHODS

This was an observational and transversal study of cardiovascular risk factors making up the MS in an adult population. 367 subjects aged 35-79 years (268 men and 99 women) were studied; 185 had CHD (141 men and 44 women) and 182 (127 men and 55 women) were included as a control population. 82 individuals of the control group who had no MS components were selected for the calculation of parameters of hyperinsulinism and the HOMA (Homeostasis Model Assessment) index in order to evaluate the insulin resistance.

RESULTS

As compared with the control group, patients with CHD showed higher blood pressure (systolic and dyastolic), body mass index (BMI), triglicerydes and apo B100 concentrations, and lower HDL-c and apo A1 values. They also exhibited higher values of glycemia and insulinemia and consequently a higher HOMA index. The values of insulin and HOMA (percentil 75), obtained from the selected group for this purpose, were 12 U/ml and 3.03, respectively. In the CHD population, 38.28% (95% CI, 31.13-45.95) had hyperinsulinism, 47.02% (95% CI, 39.70-54.47) had insulin resistance (HOMA) and 41.08% (95% CI, 33.98-48.55) had MS.

CONCLUSIONS

There was a high prevalence of cardiovascular risk factors in the CHD population. Patients with CHD have higher hyperinsulinism and insulin resistance as well as a greater prevalence of MS. Despite treatment, a clear association exists between MS and CHD in both men and women.