Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

Natural aging is accompanied by a dysregulation of the host immune response that has well-known clinical consequences but poorly defined underlying causes. It has previously been reported that advancing age is associated with an increase in membrane cholesterol level in T cells. The aim of this study was to investigate whether high-density lipoprotein (HDL) can modulate the age-related accumulation of membrane cholesterol in T cells and impact on their subsequent responsiveness. Our data reveal that cholesterol metabolism, influx, and efflux are altered in T cells with aging, which may in part explain the increase in membrane cholesterol level observed in T cells in elderly individuals. HDL was unable to promote reverse cholesterol transport in T cells from elderly subjects with the same efficiency as was observed in T cells from young subjects besides unchanged ABCA-1 and SR-BI expressions. HDL exhibited a short-acting co-stimulatory effect by enhancing T cell production of interleukin-2 (IL-2). Moreover, HDL from healthy normolipemic individuals exerted differential effects on T cell proliferation that depended on the age of the HDL donor. Finally, HDL modulated TCR/CD28 activation by inducing sustained signaling through pLck, pERK, and pAkt. These data suggest that HDL has immunomodulatory effects on T cells that are influenced by age.     

Paraoxonase-1 (PON1) activity in patients with coronary artery diseases and in diabetic patients

Cardiovascular diseases are the main cause of mortality in the world, diabetics and patients with coronary artery diseases in particular. In fact, the increase of cardiovascular risk was established in many epidemiological and clinical studies. The aim of this work is to study both the lipid profile and the enzymatic activity of PON1 in diabetics and coronary patients from Morocco (Casablanca region) along with the cardiovascular risk factors in this population. Three groups of Moroccan subjects were investigated: 36 patients with coronary artery diseases, 110 diabetic patients and 100 healthy subjects (control group). Total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (c-HDL) levels were evaluated using colorimetric methods. Low-density lipoprotein cholesterol (c-LDL) was calculated according to the Friedewald's formula. Serum activity of PON1 was measured by spectrophotometry. Compared to healthy subjects, we noted a significant decrease of PON1 activity in coronary artery disease (285?U/mL?±?180?U/mL; P?相似文献   

Paraoxonase activity in healthy, diabetic, and hemodialysis patients

ObjectivesParaoxonase 1 (PON1) is mainly complexed to HDL and is responsible, at least in part, for their antioxidant properties. The aims of our study were to determine the phenotype distribution and enzymatic activities of PON1 and the oxidative stress status of healthy subjects and diabetic and hemodialysis patients.Design and methodsPON1 paraoxonase and arylesterase activities and oxidative stress markers [malondialdehyde (MDA) and vitamin E levels] were measured in 300 individuals as a function of health status.ResultsThe prevalence of the PON1 phenotypes in the study population was 74.51%, 18.15% and 7.34% for QQ, QR and RR, respectively. The phenotype distribution did not change significantly as a function of health status (healthy, diabetes, hemodialysis). However, the hemodialysis patients had lower PON1 paraoxonase and arylesterase activities than the diabetic patients and healthy subjects, while there were no significant differences between the diabetic patients and the healthy subjects. Oxidative stress markers (MDA levels and vitamin E/cholesterol ratio) were significantly higher in the diabetic and hemodialysis patients than in the healthy subjects.ConclusionsThe lower plasma PON1 enzymatic activities in the hemodialysis patients was not associated with a difference in the phenotype distribution of PON1. Oxidative stress conditions were significantly higher in these patients, which may increase the risk of atherosclerosis in this population.     

Elastin peptides induced oxidation of LDL by phagocytic cells

The degradation products of one of the major component of vascular wall, elastin, have several important biological activities. Elastin peptides (KE) are mostly generated during vascular aging and the atherosclerotic process. They induce free radical and proteases production from cells, which are the major components of the atherosclerotic process. In the present study, we investigated whether the interaction between elastin peptides and neutrophils as well as monocytes contributes to low density lipoproteins (LDL) oxidation, being one of the most important initiator of the chronic inflammatory process contributing to the development of atherosclerosis. Here, we present data on the link between the elastin degradation products and LDL oxidation by the chemotactically attracted neutrophils and monocytes. The KE as well as the active epitope, the hexapeptide VGVAPG is able, in a differential concentration and time dependence, to induce the oxidation of LDL. KE is able to induce via the production of free radicals by neutrophils the oxidation of LDL very rapidly and in higher concentration compared to monocytes. These effects of KE are occurring through the stimulation of the 67 kDa elastin-laminin receptor (ELR), as demonstrated by the uncoupling effect of lactose. In our present study, the HDL was able to decrease the LDL oxidation by KE. This is a new mechanism by which elastin peptides might participate in the initiation and progression of the atherosclerotic process.     

Multimodal architectonic subdivision of the caudal ventrolateral prefrontal cortex of the macaque monkey

The caudal part of the macaque ventrolateral prefrontal cortex (VLPF) is part of several functionally distinct domains. In the present study we combined a cyto- and a myeloarchitectonic approach with a chemoarchitectonic approach based on the distribution of SMI-32 and Calbindin immunoreactivity, to determine the number and extent of architectonically distinct areas occupying this region. Several architectonically distinct areas, completely or partially located in the caudal VLPF, were identified. Two areas are almost completely limited to the anterior bank of the inferior arcuate sulcus, a dorsal one—8/FEF—which extends also more dorsally and should represent the architectonic counterpart of the frontal eye field, and a ventral one—45B—which occupies the ventral half of the bank. Two other areas occupy the ventral prearcuate convexity cortex, a caudal one—area 8r—located just rostral to area 8/FEF and a rostral one—area 45A—which extends as far as the inferior frontal sulcus. Area 45A borders dorsally, in the proximity of the principal sulcus, with area 46 and, ventrally, with area 12. The present data show the existence of two distinct prearcuate convexity areas (8r and 45A), extending other architectonic subdivisions of the caudal VLPF and providing a new, multiarchitectonic frame of reference for this region. The present architectonic data, together with other functional and connectional data, suggest that areas 8/FEF, 45B and 8r are part of the oculomotor frontal cortex, while area 45A is a distinct entity of the VLPF domain involved in high-order processing of nonspatial information.     

Effect of 6 months of exercise and isoflavone supplementation on clinical cardiovascular risk factors in obese postmenopausal women: a randomized, double-blind study

OBJECTIVE: To investigate whether 6 months of exercise combined with isoflavone supplementation could improve clinical risk factors that predispose to cardiovascular disease in obese postmenopausal women. DESIGN: This was a randomized, double-blind, controlled trial in which 50 healthy obese postmenopausal women were divided into two groups and assigned to isoflavone supplementation (n=25) or a placebo (n=25) for 1 year. For the last 6 months, both groups participated in an exercise program (three times per week), at the end of which cardiovascular disease risk factors were compared between groups. Body composition (using dual-energy x-ray absorptiometry), metabolic profile (blood lipids, fasting insulin, fasting glucose, sex hormone-binding globulin, C-reactive protein) were determined at baseline and at 6 and 12 months. RESULTS: We observed a significant effect of exercise and isoflavone supplementation on body weight, total and abdominal fat mass (kilograms and percentage), body mass index, appendicular fat-free mass, fat-free mass/fat mass ratio, and sex hormone-binding globulin, but not with exercise alone. No difference was observed for other biochemical characteristics, although the quantitative insulin sensitivity check index increased equally in both groups. Conversely, although not significant, we observed a tendency for a treatment effect on body mass index (P=0.07) and on absolute (kilograms) (P=0.07) and percentage of (P=0.053) abdominal fat mass, whereas no effect of treatment was found for other variables using the Mann-Whitney test. CONCLUSIONS: Compared to an aerobic exercise program alone, 70 mg/day of isoflavones combined with exercise may promote significant improvements in body composition parameters that are known to influence cardiovascular disease risk in postmenopausal women.     

Cortical connections of the anterior (F5a) subdivision of the macaque ventral premotor area F5

We traced the cortical connections of the anterior sector (F5a) of the macaque ventral premotor (PMv) area F5 and compared them with those of the adjacent F5 sectors, F5c and F5p. F5a displays a very dense “intrinsic” connectivity with F5c and F5p, premotor connections limited to F4 and F6/pre-SMA, relatively robust prefrontal connections with areas 46v and 12, and dense connections with rostral opercular frontal areas. Outside the frontal cortex, connections of F5a are dense with the SII region, relatively robust with inferior parietal areas PFG and AIP, weak with the inferior parietal area PF, and moderate with area 24. The comparison with data from injections in F5c and F5p showed that F5a, though sharing some common parietal connections with the other F5 sectors, displays several characterizing features providing robust evidence for its connectional distinctiveness. The present study provides evidence for a general organization of the PMv similar to that of the medial and dorsal premotor cortex, with F5a representing a pre-PMv area. Specifically, the present data suggest that F5a is a privileged site of integration, in the PMv, of parietal sensory-motor signals with higher-order information originating from prefrontal, rostral frontal opercular areas, and F6/pre-SMA. The results of this integration can be then broadcasted to the adjacent F5 sectors for the generation and control of hand actions and cognitive motor functions.     

Effects of vitamin C supplementation on antioxidants and lipid peroxidation markers in elderly subjects with type 2 diabetes

The objective of our study was to evaluate the effects of the administration of two dosages of vitamin C (Vit-C) (0.5 and 1g/day, vs. placebo) in elderly patients with type 2 diabetes mellitus on the intracellular levels of Vit-C and glutathione, and on the lipid peroxidation markers and vitamin E (Vit-E) content of low-density lipoprotein (LDL) and on LDL susceptibility to gamma radiolysis-induced peroxidation. Thirty-six patients were randomized into three groups. In patients on 0.5 g Vit-C/day versus the placebo group, a significant increase in cellular reduced glutathione level was observed (0.60+/-0.26 vs. 0.33+/-0.27). In patients on 1 g Vit-C/day versus placebo, a significant increase was also observed in cellular reduced glutathione (0.93+/-0.70 vs. 0.33+/-0.27), in Vit-C (5.66+/-2.00 vs. 2.72+/-1.88) and in vitamin E content of LDL (1.98+/-0.38 vs. 1.48+/-0.40). No change was observed in either group in basal levels of lipid peroxidation markers and in the susceptibility of LDL to peroxidation provoked by gamma-radiolysis. In conclusion, Vit-C has a dose-dependent effect on the cellular contents of antioxidants and on vitamin E content of LDL in elderly patients with type 2 DM. These changes are not sufficient to decrease the LDL susceptibility to peroxidation.     

Consumption of argan oil may have an antiatherogenic effect by improving paraoxonase activities and antioxidant status: Intervention study in healthy men

BACKGROUND AND AIM: Due to its high antioxidant and mono- and polyunsaturated fatty acid content virgin argan oil (VAO) could play a beneficial role in cardiovascular prevention. We were therefore interested in determining whether the consumption of VAO could improve plasma paraoxonase (PON1) activities and antioxidant status in healthy men. METHODS AND RESULTS: Sixty young men were included in this interventional study. They were given a controlled diet for 2 weeks as baseline and then received 25 g/day of butter. The group was randomised to two diet group periods of 3 weeks each. The VAO group received 25 ml/day of oil and the extra virgin olive oil (EVO) group received the same quantity of EVO as control group. Plasma PON1 activities, antioxidant vitamins and LDL susceptibility to oxidation were measured. The analysis of the results shows that PON1 activities increase significantly in both groups and that lipoperoxides and conjugated dienes formation decreases significantly in VAO and EVO groups compared to baseline values (P=0.001 and P=0.014, respectively). Vitamin E concentration increases significantly only in VAO group (P=0.007). Susceptibility of LDL to lipid peroxidation shows a significant increase in lag phase and a significant decrease in maximum diene production in VAO (P=0.005) and EVO groups (P=0.041 and P=0.005, respectively). CONCLUSIONS: Our findings confirm the beneficial effect of EVO on plasma antioxidant status and show for the first time the same effect for VAO supplementation in man. Thus, VAO offers an additional natural food supplement to reduce cardiovascular risk.