Elena Moldoveanu

Lipoprotein-associated phospholipase A2 (Lp-PLA2): a review of its role and significance as a cardiovascular biomarker

Objective: To conduct a comprehensive, systematic review of studies assessing the significance of lipoprotein-associated phospholipase A2 in cardiovascular diseases (CVDs). Material and methods: A review of the literature was performed using the search term “Lipoprotein-associated phospholipase A2 (Lp-PLA2)” and each of the following terms: “cardiovascular risk,” “cardiovascular death,” “atherosclerotic disease,” “coronary events,” “transient ischemic attack (TIA),” “stroke,” and “heart failure.” The searches were performed on Medline, Google Scholar and ClinicalTrails.gov. Results: The majority of published studies showed a significant association between Lp-PLA2 levels and cardiovascular events after multivariate adjustment. The association was consistent across a wide variety of subjects of both sexes and different ethnic backgrounds. Conclusions: The role of Lp-PLA2 as a significant biomarker of vascular inflammation was confirmed, and Lp-PLA2 seems to be closely correlated to cardiovascular events. It may be an important therapeutic target and may have an important role in prevention, risk stratification and personalised medicine.

Significance of platelet‐activating factor acetylhydrolase in patients with non‐insulin‐dependent (type 2) diabetes mellitus

Background: Non‐insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continnous low‐grade inflammation and endothelial activation state. Plasma platelet ‐ activating factor ‐ acetylhydrolases (PAF‐AHs) are a subgroup of Ca2+ ‐independent phospholipase A2 family (also known as lipoprotein‐associated phospholipases A2) that hydrolyze and inactivate the lipid mediator platelet‐activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF‐AH activity and LDL‐cholesterol/HDL‐cholesterol (LDL‐ch/HDL‐ch) ratio in NIDDM patients as compared to controls. Methods: serum PAF‐AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL‐ch, HDL‐ch, triglyceride and blood glucose were determined in all subjects. Results: All NIDDM patients display hiperlipidemia, with increased LDL‐ch and triglyceride levels. There is a significant correlation between LDL‐ch levels (especially LDL‐ch / HDL‐ch ratio) and PAF‐AH activity in dyslipidemic and NIDDM patients. Conclusion: Diabetic and dyslipidemic patients have an increased plasma PAF‐AH activity correlated with their LDL‐ch levels and mainly with LDL‐ch / HDL‐ch ratio. Plasma PAF‐AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.

Low basal levels of circulating adiponectin in patients undergoing coronary stenting predict in-stent restenosis, independently of basal levels of inflammatory markers: Lipoprotein associated phospholipase A2, and myeloperoxidase

OBJECTIVE The aim of this study was to find a pre-interventional marker with the capacity to predict in-stent restenosis (ISR). Considering the anti-atherosclerotic role of adiponectin (APO), an adipocytokine with anti-inflammatory, anti-proliferative, anti-oxidative and anti-thrombotic properties, low plasma levels of APO might be correlated with the risk of ISR. We investigated the correlations between the plasma levels of APO and two markers of inflammation: lipoprotein associated phospholipase A2 (Lp-PLA2) and myeloperoxidase (MPO). DESIGN AND METHODS 80 patients with angiographically significant stenosis underwent percutaneous coronary intervention (PCI) with bare metal stent. Plasma APO concentration and plasma Lp-PLA2 and MPO activities were evaluated immediately before and after PCI, then followed-up at 24, 48, 72 h, and at 1, 3, 6 months, respectively. ISR was evaluated at 6 months after stenting by follow-up coronary angiograms, and it was defined as >50% stenosis of the target lesion. RESULTS ISR was present in 33.75% of patients. Baseline APO plasma concentration, measured before PCI, was lower in ISR patients than those without ISR [3.97 (+/-1.05) vs 6.65 (+/-2.95) microg/mL respectively, p<0.001]. The patients with APO values less than 4.9 microg/mL at discharge were more susceptible to develop ISR (odd ratio, 4.27; 95% CI, 1.56-11.72, p<0.001). ISR rate was independent of inflammation markers Lp-PLA2 and MPO baseline values, measured before PCI. CONCLUSIONS The persistence of a low APO plasma level at discharge and 6 months afterwards may be used as a clinically useful marker for ISR prediction in patients undergoing PCI.

Antioxidant defense capacity in scleroderma patients

Abstract Background: Oxidative stress is associated with scleroderma (systemic sclerosis) and is supposed to favor disease progression by complex effects on the vascular endothelium and on fibroblasts. Methods: Plasma oxidative process marker, thiobarbituric acid-reactive substances, and several markers of antioxidant defense capacity (plasma total antioxidant activity, serum albumin, uric acid and glutathione, superoxide dismutase and catalase) were evaluated by spectrophotometric methods using blood samples collected from 23 scleroderma patients and 21 healthy controls. Results: In scleroderma patients, thiobarbituric acid-reactive substances levels (mmol/L plasma) were significantly elevated (29.3±5.8) compared with healthy controls (16.6±3.1, p<0.001). Total antioxidant activity (mmol Trolox/L) was significantly lower in scleroderma patients than in controls (1.29±0.13 vs. 1.55±0.23, p<0.001), as well as the antioxidant gap (mmol Trolox/L) (0.57±0.18 vs. 0.92±0.22, p<0.001). Superoxide dismutase activity (IU/g hemoglobin) was markedly decreased in patients as compared with controls (395±184 vs. 659±211, p<0.001). Conclusions: Lower plasma total antioxidant activity and plasma antioxidant gap in scleroderma patients show that plasma antioxidant defense is deficient in scleroderma patients. As previous studies on this issue are controversial, the decreased erythrocyte superoxide dismutase activity found in the patients in this study needs further investigation. Clin Chem Lab Med 2008;46:836–41.

Apoptotic rate in patients with myelodisplastic syndrome treated with modulatory compounds of pro‐apoptotic cytokines

Excessive apoptosis has a central role in ineffective hematopoiesis in myelodysplastic syndrome (MDS). The aim of the study was to quantify apoptosis and Bcl‐2 expression in patients with MDS and to use these parameters in the evaluation of treatment efficacy with compounds modulating proapoptotic cytokines. Bone marrow (BM) samples from eight MDS patients were studied: four with refractory anemia and four with refractory anemia with ringed sideroblasts. Two patients with Hodgkin disease without BM determination were studied for control. Therapy consisted in administration of pentoxyphylline, dexamethasone and ciprofloxacin. Biochemical assay of apoptosis and Bcl‐2 was performed using annexin V‐biotin conjugate antibody and anti‐human Bcl‐2 antibody respectively, followed by streptavidine‐peroxidase conjugate, and peroxidase substrate. Ultrastructural investigation of BM samples was performed with standard electron microscopy techniques. Most of BM hematopoietic cells in the MDS patients had ultrastructural features of various stages of apoptosis including chromatin condensation and margination, cytoplasm condensation and budding of nuclear and plasma membranes to produce apoptotic bodies. Bcl‐2 expression showed an inverse correlation with the rate of the apoptotic process. Periodic evaluation of these two parameters has shown an increase of Bcl‐2 expression and a decrease of apoptotic rate in patients who had responded to the treatment. Response to the treatment was appreciated in accordance with their transfusion needs. Treatment efficiency diminished in time. The rate of apoptosis was inversely correlated with the level of Bcl‐2 expression. These results confirm the importance of the apoptotic process evaluation in monitoring MDS treatment.

Lipoprotein-associated phospholipase A2 activity in patients with preserved left ventricular ejection fraction

Background: A significant proportion of heart failure (HF) patients have preserved ejection fraction (EF). Considering that inflammation and oxidative stress are involved in HF evolution, we investigated lipoprotein-associated phospholipase A2 (LpPLA2), an enzyme involved in these pathophysiologic processes in relation to EF. Methods and results: The study included 208 HF patients and 20 healthy controls. HF patients with preserved EF (HFpEF) represented 42.31% of all HF patients. LpPLA2 activity was significantly increased in HF patients when compared with controls and was higher in HFpEF than in HF with reduced EF patients (HFrEF). The incidence of left ventricular hypertrophy was higher in HFpEF than in HFrEF (EF < 50). Conclusion: Confirming its role as a marker of vascular inflammation, LpPLA2 seems to be a biomarker constantly correlated with HF, regardless of etiology. Elevated plasma values of LpPLA2 in HFpEF are consistent with the exacerbated inflammatory status.

The antiphospholipid antibodies.

Antiphospholipid antibodies (APLAs) are a group of autoantibodies directed against certain phospholipids, or their protein cofactors. Assay of APLAs is important because their interaction with anionic phospholipid-protein cofactors can generate a syndrome of hypercoagulability associated with a wide variety of thromboembolic events. This article presents the characteristics of some APLAs [anticardiolipin antibodies (aCLAs), lupus anticoagulant (LA) and anti-beta2-glycoprotein I antibodies (anti-beta2-GPIAs)], their action, and their interaction with blood and endothelial cells. The presence of APLAs has been reported in many diseases (autoimmune diseases, atherosclerosis, infections, malignancies), being related to pathogenic mechanisms and/or to a more severe evolution of the disease.