👤 Katia Georgopoulos

We aimed to test the effect of hydroxychloroquine (HCQ) treatment on atherosclerosis and plasma lipids in apolipoprotein E deficient (ApoE Forty-seven (47) mice were divided into two treatment groups: an HCQ group administered 10 mg/kg/day in drinking water for 16 weeks and a control group with no HCQ. All mice were maintained on a standard chow diet containing 5% fat and had free access to water. At 32 weeks of age, blood was drawn for plasma lipid determination and the proximal aorta was removed to measure the atherosclerotic area and evaluate the expression of eNOS and HIF-1α by immunohistochemistry. The HCQ group consisted of 16 mice (10 males, six females), while the control group consisted of 31 mice (17 males, 14 females). HCQ significantly reduced the atherosclerotic area (mm HCQ reduces aortic atherosclerosis in ApoE Show less

Subtle deviations in zero-lag cross correlations (synchronous neural interactions, SNI) differentiate healthy from pathological brain states. Here, we assessed blood biomarkers of dementia and neurodegeneration in relation to SNI in 175 women participating in a longitudinal study for a total of 348 acquisitions. Of seven biomarkers tested (Aβ Show less

Hydroxychloroquine (HCQ) has been associated with lower incidence of cardiovascular events in patients with autoimmune diseases and atherosclerosis progression in mouse models. Our study aimed at investigating the effect of HCQ on autophagy and neutrophil extracellular trap (NET) formation in aortas of ApoE-/- mice. ApoE-/- mice were treated with 10 mg/kg/day HCQ for 16 weeks. The aortas were examined histologically, while immunofluorescence staining and confocal microscopy were performed to identify the co-localization of myeloperoxidase (MPO) with DNA or microtubule-associated protein 1A/1B-light chain 3B (LC3B) as markers of NET formation and autophagy, respectively. Among 52 ApoE-/- mice (30 male, 22 female), HCQ was administered in 15 male and 12 female mice. HCQ was associated with a significant reduction of the mean (±SD) surface of the atherosclerotic plaque compared to controls (HCQ-treated vs. control, 0.04 ± 0.01 mm2 vs. 0.08 ± 0.04 mm2, p < 0.01 and 0.06 ± 0.04 mm2 vs. 0.15 ± 0.09 mm2, p = 0.012, for male and female, respectively). This reduction was associated with a significant attenuation in the mean fluorescence intensity of MPO and LC3B expression in the atherosclerotic plaque of HCQ-treated mice (p = 0.03 and p = 0.01, respectively). In line with these findings, HCQ significantly reduced the proportion of MPO+ and LC3B+ cells within the atherosclerotic lesions. HCQ administration in ApoE-/- mice may mitigate the progression of atherosclerotic plaque, by inhibiting autophagy and NET formation. Show less

Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs. How this occurs remains unclear. Here we demonstrate that in small pre-B cells, the lineage and stage-specific epigenetic reader bromodomain and WD repeat-containing protein 1 (BRWD1) reorders three-dimensional chromatin topology to affect the transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters, and coordinated this switch with Igk locus contraction. BRWD1 did so by converting chromatin-bound static to dynamic cohesin competent to mediate long-range looping. ATP-depletion revealed cohesin conversion to be the main energetic mechanism dictating dynamic chromatin looping. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be dictated by lineage contextual mechanisms to facilitate specific cell fate transitions. Show less

The Chennai Urban Population Study investigates a South Indian population with a high prevalence of cardiovascular disease associated with the metabolic syndrome (MS). The Ala54Thr polymorphism in the fatty acid-binding protein 2 (FABP2) gene as well as the T-455C and C-482T polymorphisms in the apolipoprotein C-III (APOC3) gene promoter have been associated with features of the MS in specific populations. This study evaluates in Asian-Indians the association between these polymorphisms with MS and dyslipidemia, defined according to National Cholesterol Education Program Adult Treatment Panel III. Allelic frequencies in 70 controls and 110 patients with diabetes from the Chennai Urban Population Study were 52.9% for FABP2 Thr54, 73.0% for APOC3 -482T, and 80.2% for APOC3 -455C. The polymorphisms were in agreement with Hardy-Weinberg equilibrium. Controls carrying FABP2 Thr54 were more likely to have MS than noncarriers (Fisher's exact test P = 0.031; odds ratio = 6.9 with a 95% confidence interval of 1.1, 43.9). Those carrying at least one polymorphic allele in both genes had a higher likelihood of having MS than wild type (Fisher's exact test P = 0.003; odds ratio = 12.1 with a 95% confidence interval of 1.88, 77.6). Dyslipidemia was associated with the polymorphism as well. The polymorphisms were not associated with MS in patients with diabetes. The association of the polymorphisms with MS and dyslipidemia could contribute to the high cardiovascular disease prevalence in this population. Show less