1.
Decreased Nuclear Ascorbate Accumulation Accompanied with Altered Genomic Methylation Pattern in Fibroblasts from Arterial Tortuosity Syndrome Patients.
Németh, CE, Nemoda, Z, Lőw, P, Szabó, P, Horváth, EZ, Willaert, A, Boel, A, Callewaert, BL, Coucke, PJ, Colombi, M, et al
Oxidative medicine and cellular longevity. 2019;:8156592
Abstract
Ascorbate requiring Fe2+/2-oxoglutarate-dependent dioxygenases located in the nucleoplasm have been shown to participate in epigenetic regulation of gene expression via histone and DNA demethylation. Transport of dehydroascorbic acid is impaired in the endomembranes of fibroblasts from arterial tortuosity syndrome (ATS) patients, due to the mutation in the gene coding for glucose transporter GLUT10. We hypothesized that altered nuclear ascorbate concentration might be present in ATS fibroblasts, affecting dioxygenase activity and DNA demethylation. Therefore, our aim was to characterize the subcellular distribution of vitamin C, the global and site-specific changes in 5-methylcytosine and 5-hydroxymethylcytosine levels, and the effect of ascorbate supplementation in control and ATS fibroblast cultures. Diminished nuclear accumulation of ascorbate was found in ATS fibroblasts upon ascorbate or dehydroascorbic acid addition. Analyzing DNA samples of cultured fibroblasts from controls and ATS patients, a lower global 5-hydroxymethylcytosine level was found in ATS fibroblasts, which could not be significantly modified by ascorbate addition. Investigation of the (hydroxy)methylation status of specific regions in six candidate genes related to ascorbate metabolism and function showed that ascorbate addition could stimulate hydroxymethylation and active DNA demethylation at the PPAR-γ gene region in control fibroblasts only. The altered DNA hydroxymethylation patterns in patient cells both at the global level and at specific gene regions accompanied with decreased nuclear accumulation of ascorbate suggests the epigenetic role of vitamin C in the pathomechanism of ATS. The present findings represent the first example for the role of vitamin C transport in epigenetic regulation suggesting that ATS is a compartmentalization disease.
2.
Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome.
Tousoulis, D, Plastiras, A, Siasos, G, Oikonomou, E, Verveniotis, A, Kokkou, E, Maniatis, K, Gouliopoulos, N, Miliou, A, Paraskevopoulos, T, et al
Atherosclerosis. 2014;(1):10-6
Abstract
OBJECTIVES Metabolic syndrome (MetS) is associated with adverse cardiovascular events, and impaired vascular function. In this study we evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on vascular function, inflammatory and fibrinolytic process in subjects with MetS. METHODS We studied the effect of a 12 weeks oral treatment with 2 g/day of omega-3 PUFAs in 29 (15 male) subjects (mean age 44 ± 12 years) with MetS on three occasions (day0: baseline, day 28 and day 84). The study was carried out on two separate arms (PUFAs and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. The diagnosis of MetS was based on the guidelines of Adult Treatment Panel III definition. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Serum levels of interleukin-6(IL-6) and plasminogen activator inhibitor-1(PAI-1) were measured by ELISA. RESULTS Treatment with PUFAs resulted in a significant improvement from day 0 to 28 and 84 in FMD and PWV (p < 0.001 for all). Nevertheless, treatment with placebo resulted in no significant changes in FMD (p = 0.63) and PWV (p = 0.17). Moreover, PUFAs treatment, compared to placebo, decreased IL-6 levels (p = 0.03) and increased PAI-1 levels (p = 0.03). Finally, treatment with PUFAs resulted in a significant decrease in fasting triglyceride levels from day 0 to 28 and 84 (p < 0.001) and in serum total cholesterol levels (p < 0.001). CONCLUSIONS In subjects with MetS, treatment with omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect.
3.
Lifestyle, cardio-metabolic risk and arterial stiffness.
Duda-Seiman, DM, Mancaş, S, Gaită, D, Drăgan, S, Velimirovici, D, Iurciuc, S, Sarău, CA, Iurciuc, M, Rada, M, Petcov, B
Romanian journal of internal medicine = Revue roumaine de medecine interne. 2008;(1):39-45
Abstract
UNLABELLED HDL-cholesterol plays a key role defining the functional state of the arteries and the relation to cardiovascular risk. AIM: To assess the degree of arterial stiffness in asymptomatic subjects with and without cardiovascular risk, depending on lipidic parameters behavior and on the insulin resistance state. METHODS Arterial stiffness was assessed using the carotid-radial pulse wave velocity (PWV-CR) measured with Complior; cardiovascular risk was calculated using the SCORE chart; metabolic risk was quantified by assessing fasting lipidic (TC, TG, HDL, LDL) and glycemic parameters (HOMA-IR >1 defines the insulin resistance state). RESULTS 58 asymptomatic subjects, 57.62 +/- 14.40 years: 46.55% with (SCORE > or = 5%) and 53.45% without (SCORE < 5%) cardiovascular risk. In subjects with SCORE < 5% and low HDL (< 40 mg/dL), PWV-CR is influenced by the TG/HDL ratio (R2=0.27, p=0.04); LDL < 115 mg/dL has a powerful influence on PWV-CR (R2=0.58, p=0.02); the association of lipidic alterations is predictive for increased PWV-CR (> or = 9.5 m/s) (R2=0.85, p=0.008). In subjects with SCORE > or = 5%, protective HDL level (> or = 40 mg/dL) and HOMA-IR > 1, PWV-CR is strongly related to the insulin resistance state (R2=0.74, p=0.02), also to the association with LDL levels (R2=0.92, p=0.01). CONCLUSIONS The association between low HDL levels and other lipidic alterations in asymptomatic subjects with low cardiovascular risk influences the degree of arterial stiffness. Increased HDL levels and the presence of insulin resistance syndrome in high risk asymptomatic subjects are predictive for arterial stiffness. This prediction is amplified by LDL association to the metabolic state of the insulin resistance syndrome. It is necessary to establish target levels for HDL and TG in the cardiovascular disease prevention guidelines.