Simultaneous Electrochemical Detection of LDL and MDA-LDL Using Antibody-Ferrocene or Anthraquinone Conjugates Coated Magnetic Beads.

The simultaneous detection of atherosclerotic cardiovascular disease (ACSVD) biomarkers was recently of great scientific interest. In this work, magnetic beads-based immunosensors for the simultaneous detection of low density lipoprotein (LDL) and malondialdehyde-modified low density lipoprotein (MDA-LDL) were presented. The approach proposed was based on the formation of two types of specific immunoconjugates consisting of monoclonal antibodies: anti-LDL or anti-MDA-LDL, together with redox active molecules: ferrocene and anthraquinone, respectively, coated on magnetic beads (MBs). The decrease in redox agent current in the concentration range: 0.001-1.0 ng/mL for LDL and 0.01-10.0 ng/mL for MDA-LDL, registered by square wave voltammetry (SWV), was observed upon the creation of complex between LDL or MDA-LDL and appropriate immunoconjugates. The detection limits of 0.2 ng/mL for LDL and 0.1 ng/mL for MDA-LDL were estimated. Moreover, the results of selectivity against the possible interferents were good, as human serum albumin (HSA) and high density lipoprotein (HDL), stability and recovery studies demonstrated the potential of platform proposed for early prognosis and diagnosis of ASCVD.

Immune complexes containing malondialdehyde (MDA) LDL induce apoptosis in human macrophages.

Immune complexes (IC) containing predominantly malondialdehyde-LDL and the corresponding autoantibodies (MDA-LDL IC) predict acute cardiovascular events, while IC rich in oxidized LDL (oxLDL IC) predict cardiovascular disease progression. Our objective was to determine mechanisms that could explain these prognostic differences. We compared the effects of the interaction of oxLDL, MDA-LDL and the corresponding IC with human macrophages focusing on apoptosis, metalloproteinases, and proinflammatory cytokines. MDA-LDL IC induced higher degrees of apoptosis, higher levels of caspase-3 expression, and increased expression and release of MMP-1 and TNF compared to MDA-LDL, oxLDL, and oxLDL IC. The pro-apoptotic effects of MDA-LDL IC were inhibited by blocking TNFR 1 or FcγRI. Blocking FcγRI abrogated the induction and expression of MMPs and proinflammatory cytokines by MDA-LDL IC. In conclusion, the interaction of MDA-LDL IC with FcγRI triggers macrophage apoptosis and increased expression and release of TNF and MMP-1, which can lead to the rupture of unstable plaques.

The Role of Natural Low Molecular Weight Dicarbonyls in Atherogenesis and Diabetogenesis.

This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not "oxidized" (lipoperoxide-containing) LDL, but dicarbonyl-modified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus.

Optimal serum phenylalanine for adult patients with phenylketonuria.

High serum phenylalanine in adult patients with phenylketonuria (PKU) causes neuropsychological and psychosocial problems that can be resolved by phenylalanine-restricted diet. Therefore, PKU patients must continue to adhere to phenylalanine-restricted diet for life, although the optimal serum phenylalanine level in later life has yet to be established. The purpose of this review was to establish the optimal serum phenylalanine level in later life of PKU patients. We evaluated oxidative stress status, nitric oxide metabolism, cholesterol-derived oxysterols, vitamin D and bone status, and magnetic resonance imaging (MRI) in adult PKU patients according to serum phenylalanine level. Oxidative stress increased markedly at serum phenylalanine of 700-800 µmol/L. Serum phenylalanine higher than 700-850 µmol/L correlated with the disturbance of nitric oxide regulatory system. Adult PKU patients had poor vitamin D status and exhibited predominance of bone resorption over bone formation. In the brain, the levels of 24S-hydroxycholesterol, a marker of brain cholesterol elimination, were low at serum phenylalanine levels exceeding 650 µmol/L. MRI studies showed high signal intensity in deep white matter on T2-weighted and FLAIR images of PKU patients with serum phenylalanine greater than 500 µmol/L, with decreased apparent diffusion coefficients. Changes in most parameters covering the entire body organs in adult PKU were almost acceptable below 700-800 µmol/L of phenylalanine level. However, the optimal serum phenylalanine level should be 500 µmol/L or less in later life for the brain to be safe.

Malondialdehyde-Modified Low-Density Lipoprotein as a Predictor of Major Adverse Limb Events after Endovascular Therapy in Patients with Lower Extremity Arterial Disease.

AIM: Adverse limb events after endovascular therapy (EVT) are a major concern. This study aimed to investigate the relationship between serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, a potentially potent indicator of atherosclerosis, and clinical outcomes after EVT in patients with lower extremity arterial disease (LEAD). METHODS: A total of 208 LEAD patients who underwent EVT and MDA-LDL measurements were retrospectively analyzed. Those with chronic limb-threatening ischemia (CLTI) were included in the CLTI subgroup (n=106). Patients were further categorized into the High or Low MDA-LDL groups according to the cut-off value calculated by receiver operating characteristic analysis. Major adverse limb events (MALE), a composite of cardiovascular death, limb-related death, major amputation, and target-limb revascularization, were evaluated. RESULTS: MALE occurred in 73 (35%) patients. The median follow-up interval was 17.4 months. The MDA-LDL cut-off values were 100.5 U/L (area under the curve [AUC] 0.651) in the overall population and 98.0 U/L (AUC 0.724) in the CLTI subgroup. Overall, the High MDA-LDL group showed significantly higher total cholesterol (189.7±37.5 mg/dL vs. 159.3±32.0 mg/dL, p＜0.01), low-density lipoprotein cholesterol (114.3±29.7 mg/dL vs. 87.3±25.3 mg/dL, p＜0.01), and triglyceride (166.9±91.1 mg/dL vs. 115.8±52.3 mg/dL, p＜0.01) than the Low MDA-LDL group. Multivariate Cox regression analyses revealed that MDA-LDL and C-reactive protein were independent predictors of MALE. In the CLTI subgroup, MDA-LDL was an independent predictor of MALE. The High MDA-LDL group showed worse MALE-free survival rates than the Low MDA-LDL group in overall (p＜0.01) and in the CLTI subgroup (p=0.01). CONCLUSIONS: Serum MDA-LDL level was associated with MALE after EVT.

MDA-LDL vaccination induces athero-protective germinal-center-derived antibody responses.

Atherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction, and stroke and is the leading cause of mortality worldwide. Immunization of pro-atherogenic mice with malondialdehyde-modified low-density lipoprotein (MDA-LDL) neo-antigen is athero-protective. However, the immune response to MDA-LDL and the mechanisms responsible for this athero-protection are not completely understood. Here, we find that immunization of mice with MDA-LDL elicits memory B cells, plasma cells, and switched anti-MDA-LDL antibodies as well as clonal expansion and affinity maturation, indicating that MDA-LDL triggers a bona fide germinal center antibody response. Further, Prdm1fl/flAicda-Cre+/kiLdlr-/- pro-atherogenic chimeras, which lack germinal center-derived plasma cells, show accelerated atherosclerosis. Finally, we show that MDA-LDL immunization is not athero-protective in mice lacking germinal-center-derived plasma cells. Our findings give further support to the development of MDA-LDL-based vaccines for the prevention or treatment of atherosclerosis.

The Placebo-Controlled Effect of Percutaneous Coronary Intervention on Exercise Induced Changes in Anti-Malondialdehyde-LDL Antibody Levels in Stable Coronary Artery Disease: A Substudy of the ORBITA Trial.

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significant component of oxidised LDL. The effects of exercise on levels of MDA-LDL and anti-MDA-LDL antibodies are not well-understood. Furthermore, it is not known whether these can be modified in patients with coronary artery disease by percutaneous coronary intervention (PCI). Methods: The Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multi-centre randomised trial of PCI vs. placebo procedure for angina relief. Serum samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2) exercise and post-randomisation (6-weeks following the PCI or placebo procedure), pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developed assays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies. Results: One hundred ninety-six of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severe single vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial had blood available for analysis. With exercise at pre-randomisation (P2-P1) there was no significant change in adjusted MDA-LDL (-0.001, 95% CI -0.004 to 0.001; p = 0.287); however, IgG and IgM anti-MDA-LDL significantly declined (-0.022, 95% CI -0.029 to -0.014, p < 0.0001; -0.016, 95% CI -0.024 to -0.008, p = 0.0002, respectively). PCI did not have a significant impact on either the pre-exercise values (P3 controlling for P1) of MDA-LDL (p = 0.102), IgG (p = 0.444) or IgM anti-MDA-LDL (p = 0.909). Nor did PCI impact the exercise induced changes in these markers (P4 controlling for P1, P2, and P3) for MDA-LDL (p = 0.605), IgG (p = 0.725) or IgM anti-MDA-LDL (p = 0.171). Pre-randomisation ischaemia on stress echo did not impact these interactions. Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies in patients with severe single vessel coronary disease, possibly indicating an induction in homoeostatic clearance via the innate immune system. However, PCI did not ameliorate this effect.

Coronary lipid-rich plaque characteristics in Japanese patients with acute coronary syndrome and stable angina: A near infrared spectroscopy and intravascular ultrasound study.

BACKGROUND: Asians have a much lower incidence of adverse coronary events than Caucasians. We sought to evaluate the characteristics of coronary lipid-rich plaques (LRP) in Asian patients with acute coronary syndrome (ACS) and stable angina (SA). We also aimed to identify surrogate markers for the extent of LRP. METHODS: We evaluated 207 patients (ACS, n = 75; SA, n = 132) who underwent percutaneous coronary intervention under near infrared spectroscopy intravascular ultrasound (NIRS-IVUS). Plaque characteristics and the extent of LRP [defined as a long segment with a 4-mm maximum lipid-core burden index (maxLCBI4mm)] on NIRS in de-novo culprit and non-culprit segments were analyzed. RESULTS: The ACS culprit lesions had a significantly higher maxLCBI4mm (median [interquartile range (IQR)]: 533 [385-745] vs. 361 [174-527], p < 0.001) than the SA culprit lesions. On multivariate logistic analysis, a large LRP (defined as maxLCBI4mm ≥ 400) was the strongest independent predictor of the ACS culprit segment (odds ratio, 3.87; 95% confidence interval, 1.95-8.02). In non-culprit segments, 19.8% of patients had at least one large LRP without a small lumen. No significant correlation was found between the extent of LRP and systematic biomarkers (hs-CRP, IL-6, TNF-α), whereas the extent of LRP was positively correlated with IVUS plaque burden (r = 0.24, p < 0.001). CONCLUSIONS: We confirmed that NIRS-IVUS plaque assessment could be useful to differentiate ACS from SA culprit lesions, and that a threshold maxLCBI4mm ≥ 400 was clinically suitable in Japanese patients. No surrogate maker for a high-risk LRP was found; consequently, direct intravascular evaluation of plaque characteristics remains important.

B Cells in Atherosclerosis: Mechanisms and Potential Clinical Applications.

Because atherosclerotic cardiovascular disease is a leading cause of death worldwide, understanding inflammatory processes underpinning its pathology is critical. B cells have been implicated as a key immune cell type in regulating atherosclerosis. B-cell effects, mediated by antibodies and cytokines, are subset specific. In this review, we focus on elaborating mechanisms underlying subtype-specific roles of B cells in atherosclerosis and discuss available human data implicating B cells in atherosclerosis. We further discuss potential B cell-linked therapeutic approaches, including immunization and B cell-targeted biologics. Given recent evidence strongly supporting a role for B cells in human atherosclerosis and the expansion of immunomodulatory agents that affect B-cell biology in clinical use and clinical trials for other disorders, it is important that the cardiovascular field be cognizant of potential beneficial or untoward effects of modulating B-cell activity on atherosclerosis.

Increase in oxidized low-density lipoprotein level according to hyperglycemia in patients with cardiovascular disease: A study by structure equation modeling.

AIMS: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) level has been reported to be strongly associated with the pathogenesis of cardiovascular diseases. We focused on diabetic status and investigated its possible contribution to MDA-LDL level. METHODS: The study sample consisted of 2705 patients who were admitted to our hospital and underwent cardiac catheterization. Blood samples were obtained to measure the levels of fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, LDL, MDA-LDL and others. Body mass index (BMI) was also used in constructing structural equation modeling and Bayesian estimation. RESULTS: To explore the factors theoretically associated with MDA-LDL level, we performed structural equation modeling. We generated a path model that revealed that BMI, LDL level and FBS were significantly associated with MDA-LDL level (P < 0.001 for each factor), whereas insulin level and HbA1c level were not significantly associated (P = NS for both factors). Noted above was clearly demonstrated on the image of 2-D contour line by Bayesian structure equation modeling. CONCLUSIONS: This study clearly showed that hyperglycemia affects MDA-LDL level. An interaction between diabetes and dyslipidemia was shown in terms of activation of lipid oxidation.

Modified LDL Immune Complexes and Cardiovascular Disease.

Modified forms of LDL, both spontaneously formed in the organism or prepared in the laboratory, are immunogenic. As a consequence, antigen-antibody complexes (immune complexes, IC) formed in vivo can be measured in the peripheral blood, and their levels are strong predictors of cardiovascular disease (CVD). It has been possible to generate antibodies that recognize different LDL modifications, allowing the analysis of circulating IC constitution. Clinical studies showed that the antigenic constitution of the IC has a modulating effect on the development of CVD. Patients whose IC react strongly with antibodies to copper oxidized LDL (oxLDL) show progressive development of atherosclerosis as demonstrated by increased intima-media thickness and increased coronary calcification scores. In contrast, patients whose IC react strongly with antibodies to the heavily oxidized malondialdehyde LDL prepared in vitro (MDA-LDL) are at a high risk of acute vascular events, mainly myocardial infarction. In vitro studies have shown that while oxLDL IC induce both cell proliferation and mild to moderate macrophage apoptosis, MDA-LDL IC induce a more marked macrophage apoptosis but not cell proliferation. In addition, MDA-LDL IC induce the release of higher levels of matrix metalloproteinases and TNF than oxLDL IC. High levels of TNF are likely to be a major factor leading to apoptosis and high levels of metalloproteinases are likely to play a role in the thinning of the fibrous cap of the atheromatous plaque. The combination of apoptosis and fibrous cap thinning is a well-known characteristic of vulnerable plaques, which are more prone to rupture and responsible for the majority of acute cardiovascular events.

Circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) as a novel predictor of clinical outcome after endovascular therapy in patients with peripheral artery disease (PAD).

BACKGROUND AND AIMS: Despite advances in the treatment of peripheral artery disease (PAD), cardiovascular events and death rates remain high. This study aimed at identifying markers of outcome in patients with PAD undergoing endovascular therapy (EVT). METHODS: Consecutive patients undergoing EVT were recruited. Markers of oxidative stress (malondialdehyde-modified low-density lipoprotein [MDA-LDL]), inflammation (IL-6; high-sensitivity C-reactive protein [hsCRP]) and fibrinolysis (D-dimer) were measured pre-EVT and at post-EVT time-points to 36 h. Clinical follow-up assessed major cardiovascular and/or limb events. RESULTS: In the 35 patients enrolled, mean MDA-LDL levels decreased from a baseline level of 106.2 U/L to 72.6 U/L immediately post-EVT (p<0.0001); levels remained significantly reduced at all time-points. IL-6, hsCRP and D-dimer increased and were significantly higher at the 36 h time-point. A significant, negative association was seen between decreased MDA-LDL and pre-EVT hsCRP levels (r = -0.42, p=0.012). Clinical follow-up data were obtained for a mean period of 16 months. MDA-LDL ratios (obtained by comparison of post- and pre-EVT values) allowed assessment of high (≥0.495) and low (<0.495) ratio groups. A significantly higher rate of major adverse events, including limb-related events or death, was seen in the low ratio group (p<0.001). Cox proportional hazard analysis including traditional risk factors indicated that this ratio is a significant predictor of clinical endpoints (HR = 0.4210, p=0.0154). An association with clinical outcome was not observed with the other candidate biomarkers. CONCLUSIONS: Assessment of pre- and post-EVT MDA-LDL levels is a promising marker of clinical outcome in patients with PAD.

High levels of AGE-LDL, and of IgG antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL in circulating immune complexes predict macroalbuminuria in patients with type 2 diabetes.

BACKGROUND: Circulating immune complexes (IC) containing modified forms of LDL (mLDL) are strongly pro-inflammatory and when present in high levels are associated with the development of diabetic complications. OBJECTIVE: We investigated whether levels of oxidized LDL (oxLDL), malondialdehyde-LDL (MDA-LDL) and advanced glycation end products-LDL (AGE-LDL) as well as IgG and IgM antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL isolated from circulating IC were associated with progression to macroalbuminuria in type 2 diabetes (VADT cohort). METHODS: Levels of mLDL in IC were measured in 905 patients, a median of two years after entry into the study. Participants were followed for an average of 3.7years for renal outcomes. Generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, persistent micro- (ACR ≥30), incident micro- (ACR ≥30) and incident macroalbuminuria (ACR ≥300) were the outcomes of interest. RESULTS AND CONCLUSIONS: Patients with macro (n=78) or non-persistent microalbuminuria (n=81) at baseline were excluded. Odds ratios for endpoints in relation to high versus low (defined using a median split) biomarker levels are found in Fig. 1. Our study demonstrates that high levels of AGE-LDL as well as of IgG antibodies (but not IgM antibodies) reacting with MDA-LDL lysine epitopes in circulating IC predict the development of macroalbuminuria in patients with type 2 diabetes. These data support the pathogenic role of modified LDL IgG antibodies but not the protective role of modified LDL IgM antibodies.

Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project.

INTRODUCTION: A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would enhance development of psychosis prevention interventions. METHODS: The North American Prodrome Longitudinal Study project is a multisite endeavor that aims to better understand predictors and mechanisms for the development of psychosis. In this study, we measured expression of plasma analytes reflecting inflammation, oxidative stress, hormones, and metabolism. A "greedy algorithm" selected analytes that best distinguished persons with clinical high-risk symptoms who developed psychosis (CHR-P; n = 32) from unaffected comparison (UC) subjects (n = 35) and from those who did not develop psychosis during a 2-year follow-up (CHR-NP; n = 40). RESULTS: The classifier included 15 analytes (selected from 117), with an area under the receiver operating curve for CHR-P vs UC of 0.91 and CHR-P vs CHR-NP of 0.88. Randomly scrambled group membership followed by reconstructions of the entire classifier method yielded consistently weak classifiers, indicating that the true classifier is highly unlikely to be a chance occurrence. Such randomization methods robustly imply the assays contain consistent information distinguishing the groups which was not obscured by the data normalization method and was revealed by classifier construction. These results support the hypothesis that inflammation, oxidative stress, and dysregulation of hypothalamic-pituitary axes may be prominent in the earliest stages of psychosis. CONCLUSION: If confirmed in other groups of persons at elevated risk of psychosis, a multiplex blood assay has the potential for high clinical utility.

SYK regulates macrophage MHC-II expression via activation of autophagy in response to oxidized LDL.

Adaptive immunity, which plays an important role in the development of atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent antigen presentation. In atherosclerotic lesions, macrophages constitute an important class of antigen-presenting cells that activate adaptive immune responses to oxidized low-density lipoprotein (OxLDL). It has been reported that autophagy regulates adaptive immune responses by enhancing antigen presentation to MHC class II (MHC-II). In a previous study, we have demonstrated that SYK (spleen tyrosine kinase) regulates generation of reactive oxygen species (ROS) and activation of MAPK8/JNK1 in macrophages. Because ROS and MAPK8 are known to regulate autophagy, in this study we investigated the role of SYK in autophagy, MHC-II expression and adaptive immune response to OxLDL. We demonstrate that OxLDL induces autophagosome formation, MHC-II expression, and phosphorylation of SYK in macrophages. Gene knockout and pharmacological inhibitors of NOX2 and MAPK8 reduced OxLDL-induced autophagy. Using bone marrow-derived macrophages isolated from wild-type and myeloid-specific SYK knockout mice, we demonstrate that SYK regulates OxLDL-induced ROS generation, MAPK8 activation, BECN1-BCL2 dissociation, autophagosome formation and presentation of OxLDL-derived antigens to CD4(+) T cells. ldlr(-/-) syk(-/-) mice fed a high-fat diet produced lower levels of IgG to malondialdehyde (MDA)-LDL, malondialdehyde-acetaldehyde (MAA)-LDL, and OxLDL compared to ldlr(-/-) mice. These results provide new insights into the mechanisms by which SYK regulates MHC-II expression via autophagy in macrophages and may contribute to regulation of adaptive immune responses in atherosclerosis.

Positive correlation between malondialdehyde-modified low-density lipoprotein cholesterol and vascular inflammation evaluated by 18F-FDG PET/CT.

OBJECTIVE: The purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT). METHODS/RESULTS: The study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, (18)F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized (18)F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0-147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values. CONCLUSION: The present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by (18)F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.

Relationship between oxidized LDL, IgM, and IgG autoantibodies to ox-LDL levels with recurrent cardiovascular events in Swedish patients with previous myocardial infarction.

We determined whether plasma levels of circulating oxidized low-density lipoprotein (LDL; E06), immunoglobulin (Ig) G, and IgM autoantibodies binding to malonyldialdehyde-modified LDL (MDA-LDL) may predict cardiovascular events (CVEs). Patients (n=123) with a previous myocardial infarction (MI) were included. The primary end point was defined as any of the following: cardiovascular death from any cause, nonfatal reinfarction or stroke, percutaneous coronary intervention, coronary artery bypass grafting, and hospitalization due to angina pectoris. There were 43 CVEs during the follow-up period of 8.4±3.5 years. There was no significant difference in the levels of E06 and MDA-LDL IgG between the CVE and the event-free group. However, MDA-LDL IgM levels were significantly lower in patients in the CVE group (9524±6326 relative light unit [RLU]) compared with the event-free (10,975±5398 RLU) group (P=.04). In conclusion, levels of MDA-LDL IgM were associated with an increased risk of CVE in patients with a previous MI.

The apolipoprotein B concentration in gingival crevicular fluid increases in patients with diabetes mellitus.

OBJECTIVE: Oral health conditions have a significant relationship with diabetes mellitus (DM) as well as dyslipidemia. In this study, we investigated the levels of apolipoprotein B (apoB) and oxidized low-density lipoprotein (oxLDL) in the gingival crevicular fluid (GCF) from patients with DM. METHODS: GCF and blood samples from 18 DM patients and 18 healthy subjects were examined. GCF was collected with paper points without inflicting any harm. The apoB and oxLDL levels were measured by sandwich ELISA assays. RESULTS: The number of teeth with a deep probing pocket depth and the number of teeth with bleeding on probing, two typical periodontal parameters, correlated with the DM parameters, such as hemoglobin A1c. The GCF volume and the concentrations of protein, apoB and oxLDL in GCF were significantly higher in the DM patients than in the healthy subjects. In particular, the apoB concentration in GCF was increased 6-fold in the DM patients. The GCF apoB concentration correlated well with the DM parameters in plasma. CONCLUSION: GCF could be a clinical source for examining not only the oral status of patients, but also certain systemic conditions.

Effect of Simvastatin on Plasma Malondialdehyde LDL (MDA-LDL) and Pregnancy-Associated Plasma Protein (PAPP-A) in Patients of Coronary Heart Disease / 中华高血压杂志

Objective To examine plasma levels of MDA-LDL and pregnancy-associated plasma protein-A in patients with angiography type lesions Ⅱ(representing plaque rupture with or without thrombosis), and to evaluate the effect of simvastatin on plasma MDA-LDL and PAPP-A. Methods One hundred and ten patients were enrolled and underwent coronary angiography with 85 patients diagnosed as coronary heart disease (CHD) and twenty-five as controls. According to the morphologic types of plaque, the patients with CHD were straitified as type Ⅰ(smooth borders) (n=31) and type Ⅱ(irregular lesions) (n=35) and type Ⅲ (long lesions with irregular surface) group (n=19). The patients in type Ⅱ group received simvastatin (40 mg/d ) for four weeks. The plasma MDA-LDL, PAPP-A, LDL, HDL levels before and after simvastatin treatment were determined. Results Plasma levels of MDA-LDL, PAPP-A in type Ⅱ group was significantly higer than that in the controls group, type Ⅰ group, type Ⅲ group (P