Although high-density lipoprotein is atheroprotective, it can become dysfunctional in chronic inflammatory conditions and increase cardiovascular risk. We previously demonstrated that HDL from subjects with documented coronary artery disease is dysfunctional and is pro-oxidant/proinflammatory in macrophages. Here we examined the influence of dysfunctional/proinflammatory HDL (piHDL) on lipid accumulation in human macrophages, in comparison to functional HDL (nHDL). Exposure of macrophages to piHDL, in contrast to nHDL, resulted in oxidative stress and marked uptake of lipids from piHDL, leading to the formation of foam cell phenotype as noted by oil red O staining with concomitant increase in total cellular cholesterol content. Using western blotting, we identified that piHDL profoundly upregulated the expression of scavenger receptor CD36 and suppressed the expression of ABCG1 and SRB1 in macrophages, thereby facilitating cholesterol influx capacity of macrophages. We then identified that CD36 did not act alone, indeed it was activated in macrophages along with ERK/MAPK, in response to piHDL, which in turn led to lipid accumulation as well as proinflammatory response via activation of NFkB and subsequent release of proinflammatory markers-TNF-ά and MMP-9. These effects were confirmed using pharmacological inhibitors for either CD36 or ERK/MAPK. Furthermore, piHDL treatment moderately activated PPAR-γ and Nrf2, the known regulators of CD36 in macrophages, suggesting that the two forms of HDL differentially regulate CD36 expression. Taken together, the results demonstrate that a novel CD36-ERK/MAPK-dependent mechanism is involved in macrophage lipid accumulation by piHDL, there by revealing the importance of functional deficiency in HDL and its potential link to atherogenesis.

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Background:Lipid peroxidation is an indicator of free radical metabolism and oxidative stress in human beings and other organisms. Malondialdehyde (MDA), an end product of lipid peroxidation, is a metabolite that can be readily estimated in serum samples. Excess oxidative stress may be a final common pathway through which anti epileptic drugs may exert their teratogenic potential in pregnant women with epilepsy. Our objective in this study was to ascertain the variations in malondialdehyde (MDA) in women with epilepsy.Material and Methods:This study was carried out in the Kerala Registry of Epilepsy and pregnancy after obtaining clearance from the Institutional Ethics Committee. Informed consent was obtained from all the subjects. The quantitative examination of MDA was performed according to standard procedures. The ideal plasma level of MDA is below 2 nmol/ml.Results:Fifteen women with confirmed epilepsy (mean age 26.9 ± 3.5) were included in the study. Two women were pregnant. MDA levels ranged from 1.7 to 2.8 nmol/ml (mean level = 2.13 ± 0.37 nmol/ml). Eight women (53 %) had MDA levels above the upper limit of normal. Three patients had levels above 2.5 nmol/ml, which corresponded to the 75 centile.Conclusions:This study had shown that the estimation of MDA levels in plasma is a convenient method to study lipid peroxidation and thereby oxidative stress in women with epilepsy. Over half of Women With Epilepsy (WWE) have excess oxidative stress as indicated by high levels of MDA in the plasma. Correlations between MDA level and characteristics of epilepsy, AED therapy, nutritional status and other medical conditions need to be observed in a larger cohort.

Background: Symptomatic intracranial atherosclerotic disease (sICAD) is associated with risk of recurrence of cerebral ischemic events in 4-19% of stroke patients annually. Previous studies indicate elevated high-sensitivity C-Reactive Protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) to be associated with risk of recurrence. Objective: This prospective, observational study investigated serum levels of hs-CRP and the activity of Lp-PLA2 in patients with sICAD in predicting the risk of long-term stroke recurrence. Methods: We enrolled 48 patients with sICAD at 3 months from onset. The demographics, clinical and imaging characteristics were recorded. Serum hs-CRP and Lp-PLA2 activity were assessed using automated high-sensitivity C-reactive protein assay and photometric technique, respectively. Patients were followed up at 6 months and 1 year and presence of new vascular events were recorded. Results: The mean age of our study population was 59.5 ± 10.3 years and 91.7% were men. Four patients developed recurrent strokes during follow-up. The mean Hs-CRP was elevated in patients with events than in patients without events (5.9 ± 10.4 mg/L vs. 1.7 ± 2.4 mg/L, P=0.03). However, there was no significant association of mean Lp-PLA2 activity (118.3±42.9 nmol/min/ml vs. 111.9 ± 34.2 nmol/min/ml, P=0.73) with recurrence. Elevation of hs-CRP (3.02 ± 4.8 mg/L vs. 0.95 ± 0.57mg/L, P=0.02) and Lp-PLA2 activity (120.1±40.3 nmol/min/ml vs. 103.3 ± 23.9 nmol/min/ml, P=0.04) was correlated with high-grade stenosis in these patients. Conclusion: Our study suggests serum levels of hs-CRP may serve as a predictor of long-term stroke recurrence risk in sICAD and elevation of hs-CRP and Lp-PLA2 correlated with the severity of stenosis in symptomatic intracranial atherosclerotic disease.