Background: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDLcholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis.Methods: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colonystimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay. Results: Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls.Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls. Conclusion:Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS.
Autonomic dysfunction is commonly detected in patients with multiple sclerosis (MS). However, data evaluating autonomic nervous system function in early MS are limited. Present study investigates response to two different stressors in newly diagnosed MS patients, looking for the signs of autonomic dysfunction at the beginning of the disease. We examined 19 MS patients and 19 age, sex, and body mass index matched healthy controls. MS patients were newly diagnosed, untreated, and with low expanded disability status scale (EDSS) values [median 1.0 (interquartile range 1.0-1.5)]. Two stressors were used to evaluate the response of autonomic nervous system: Stroop word-color interference mental stress test and orthostasis. Plasma levels of epinephrine and norepinephrine, blood pressure (BP), and heart rate variability (HRV) parameters were evaluated. At the end of Stroop test MS patients had lower systolic BP (121 ± 15 vs. 132 ± 17 mmHg, p = 0.044), lower heart rate (79 ± 9 vs. 88 ± 16 1/min, p = 0.041), and lower epinephrine increment (10 ± 22 vs. 30 ± 38 pg/ml; p = 0.049) compared to healthy controls. Norepinephrine response was unaffected in MS, however, with lower norepinephrine levels during the test (p = 0.036). HRV parameters were similar in both groups. No differences in BP, heart rate, catecholamines, and HRV parameters between groups during orthostatic testing were found. We found slightly diminished sympathetic response to mental stress test, but unchanged response to orthostasis, in newly diagnosed untreated MS patients. The results suggest that autonomic dysfunction in MS is connected with more developed disease.
Objectives. Increased metabolic and cardiovascular morbidity has been reported in multiple sclerosis (MS) patients. Previously, we have found decreased insulin sensitivity and hyperinsulinemia in a group of newly diagnosed MS patients. We hypothesize that these features may be associated with an altered lipid profile and low, intermediate, or high density lipoprotein (LDL, IDL, HDL) subclasses accelerating atherosclerosis and thus contributing to the cardiovascular risk increase in these patients.Subjects and methods. In a group of 19 newly diagnosed untreated MS patients with previously found hyperinsulinemia and insulin resistance and a matched group of 19 healthy controls, the lipoprotein subclasses profile was determined. Polyacrylamide gel electrophoresis was used to separate and measure the LDL (large LDL and small dense LDL), HDL (large, intermediate and small), and IDL (A, B and C) subclasses with the Lipoprint© System (Quantimetrix Corporation, Redondo Beach, CA, USA).Results. No difference was found either in the conventional lipid or lipoprotein subclasses profile between the MS patients and healthy controls. We found an inverse association between the level of IDL-B with fasting insulin (r=–0.504, p=0.032), the insulin resistance estimated by homeo-static model assessment – insulin resistance (HOMA-IR) (r=–0.498, p=0.035), insulin response expressed as area under the curve (AUC; r=–0.519, p=0.027), and area above the baseline (AAB; r=–0.476, p=0.045) and positive association with insulin sensitivity estimated by insulin sensitivity index (ISI) Matsuda (r=0.470, 0.048) in MS patients, but not in healthy controls suggesting the first signs in lipoprotein subclasses profile change.Conclusions. Our data indicate that changes in lipoprotein profile and subclasses are preceded by insulin resistance and hyperinsulinemia in patients with newly diagnosed MS.
Obstructive sleep apnea syndrome (OSA) is associated with increased vascular morbidity. Accelerated atherosclerosis might be one of the most important mechanisms linking OSA with the development of vascular disorders. Homocysteine (HCY) and vitamin D has been associated with atherogenesis. The aim of this study was to assess a possible association between the levels of HCY and vitamin D and the carotid intima-media thickness (cIMT), which is a known marker for subclinical atherosclerosis in patients with OSA. We prospectively enrolled 110 patients with the history of snoring, who underwent standard overnight polysomnography. Clinical characteristics of the population were recorded on admission and blood samples were obtained in the fasting condition following morning. Extracranial cIMT measurements were performed according to the standardized scanning protocol. A significant correlation was found between cIMT and apnea-hypopnea index (r = .276, p = .006), age (r = .486, p < .001), diabetes mellitus (r = .377, p < .001), coronary artery disease (r = .274, p = .006) and history of stroke (r = .251, p = .012). We failed to find any significant correlation between cIMT and the levels of HCY (r = .036, p = .724) or vitamin D (r = .027, p = .800). In conclusion, our data suggest that the association of cIMT with the severity of OSA can be influenced by multiple metabolic consequences of OSA including traditional and non-traditional risk factors. HCY and vitamin D do not seem to play a superior role in this process.
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