Ozgur Aydin

High Density Lipoprotein and it's Dysfunction

Plasma high-density lipoprotein cholesterol(HDL-C) levels do not predict functionality and composition of high-density lipoprotein(HDL). Traditionally, keeping levels of low-density lipoprotein cholesterol(LDL-C) down and HDL-C up have been the goal of patients to prevent atherosclerosis that can lead to coronary vascular disease(CVD). People think about the HDL present in their cholesterol test, but not about its functional capability. Up to 65% of cardiovascular death cannot be prevented by putative LDL-C lowering agents. It well explains the strong interest in HDL increasing strategies. However, recent studies have questioned the good in using drugs to increase level of HDL. While raising HDL is a theoretically attractive target, the optimal approach remains uncertain. The attention has turned to the quality, rather than the quantity, of HDL-C. An alternative to elevations in HDL involves strategies to enhance HDL functionality. The situation poses an opportunity for clinical chemists to take the lead in the development and validation of such biomarkers. The best known function of HDL is the capacity to promote cellular cholesterol efflux from peripheral cells and deliver cholesterol to the liver for excretion, thereby playing a key role in reverse cholesterol transport (RCT). The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High antioxidant and anti-inflammatory activities of HDL are associated with protection from CVD. This review addresses the current state of knowledge regarding assays of HDL functions and their relationship to CVD. HDL as a therapeutic target is the new frontier with huge potential for positive public health implications.

Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis

The endothelium is the primary target for biochemical or mechanical injuries caused by the putative risk factors of atherosclerosis. Endothelial dysfunction represents the ultimate link between atherosclerotic risk factors that promote atherosclerosis. HDL-C is thought to exert at least some parts of its antiatherogenic facilities via stimulating endothelial NO production, nearby inhibiting oxidative stress and inflammation. HDL-C is capable of opposing LDLs inductive effects and avoiding the ox-LDLs inhibition of eNOS. Paraoxonase 1 (PON1) is an HDL-associated enzyme esterase which appears to contribute to the antioxidant and antiatherosclerotic capabilities of HDL-C. “Healthy HDL,” namely the particle that contains the active Paraoxonase 1, has the power to suppress the formation of oxidized lipids. “Dysfunctional HDL,” on the contrary, has reduced Paraoxonase 1 enzyme activity and not only fails in its mission but also potentially leads to greater formation of oxidized lipids/lipoproteins to cause endothelial dysfunction. The association of HDL-C PON1 and endothelial dysfunction depends largely on the molecules with exact damaging effect on NO synthase coupling. Loss of nitric oxide bioavailability has a pivotal role in endothelial dysfunction preceding the appearance of atherosclerosis. Analyses of HDL-C and Paraoxonase1 would be more important in the diagnosis and treatment of atherosclerosis in the very near future.

Increased levels of total oxidant status and decreased activity of arylesterase in migraineurs.

OBJECTIVES There is strong evidence associating migraine with a variety of comorbid disorders, including cardiovascular disease and stroke, in which oxidative stress seems to be an important underlying mechanism. The aim of the study was to investigate in migraineurs the body oxidant/antioxidant balance and paraoxonase enzyme activities as a measure of HDL functionality. DESIGN AND METHODS Oxidative stress index, total oxidant status and antioxidant status were examined in addition to the paraoxonase and arylesterase enzyme activities in sixty-two migraineurs and fifty healthy control subjects. RESULTS Serum arylesterase activities were significantly lower in migraineurs (p=0.0065), whereas total oxidant status was higher in patients compared to the controls (p=0.0035). CONCLUSIONS This preliminary study showed that oxidative/antioxidative balance shifted towards the oxidative status in migraine. Moreover, the results also suggested that decreased arylesterase activities might be associated with HDL-related disfunction.

Enhanced HDL-cholesterol-associated anti-oxidant PON-1 activity in prostate cancer patients.

Increases in the generation of reactive oxygen species and decreases in antioxidant enzyme activities with aging have been reported in the prostate, and are also observed in age‐related disorders such as atherosclerosis, Alzheimers disease, and cataracts. Several studies have demonstrated that proteins are targets for reactive oxidants in cells, and that oxidized proteins accumulate during aging, oxidative stress and in some pathological conditions. However, only a limited number of studies have actually evaluated oxidative damage in relation to HDL‐cholesterol‐associated antioxidant enzyme activities or have assessed its relationship with prostate cancer. In this study, we examined the effect of HDL‐cholesterol‐associated antioxidant enzyme activities, paraoxonase1, arylesterase and new oxidative stress parameters (total oxidant status, total antioxidant status [and oxidative stress index]) in newly‐diagnosed prostate cancer patients and healthy controls. There were no significant differences in oxidative stress parameters and lipid parameters between prostate cancer patients and controls, however, paraoxonase1 enzyme activity, and non‐HDL‐cholesterol levels were higher in prostate cancer patients than controls. The results of this study were derived from a small number of subjects, but might represent an important working hypothesis for further research in a larger number of cases to clarify the role of paraoxonase1 overproduction on the prostate and its clinical relevance.

Irisin as an early marker for predicting gestational diabetes mellitus: a prospective study

Abstract Objective: The objective of this study is to evaluate maternal serum irisin levels in the first and second trimesters of pregnancy in women diagnosed with and without gestational diabetes mellitus (GDM). Methods: We performed a prospective, nested case–control study in 258 pregnant women who were enrolled at the time of the first prenatal visit (6–11th weeks of gestation) and followed until delivery. Among the entire population, we selected 20 women who subsequently developed GDM and 30 women with uneventful pregnancies. Blood samples were collected once from each participant at 6–11th weeks of gestation during the fetal viability scan and at 24–28th weeks of gestation during screening for GDM. Results: In the first trimester, irisin levels were significantly lower in women who later developed GDM (median = 453 ng/mL, range: 257–811 ng/mL) than in controls (median = 721 ng/mL, range: 700–786 ng/mL). In the second trimester, the difference in irisin levels between the GDM group (median = 749 ng/mL; range: 456–910 ng/mL) and controls (median = 757 ng/mL; range: 703–898 ng/mL) was not statistically significant. Conclusions: Irisin may be a useful biomarker in early pregnancy to predict the development of GDM.

Ischemia modified albumin is an indicator of oxidative stress in multiple sclerosis.

Introduction: Oligodendrocytes need iron in processes of energy generation and myelination. However, excessive levels of iron may exert iron induced oxidative stress and thus lead to tissue degeneration. Monitoring oxidative stress will be of paramount importance in follow-up of patients with many diseases including multiple sclerosis (MS). The aim of this study was to measure total anti-oxidative status (TAS), total oxidative status (TOS) and ischemia modified albumin (IMA) in stable relapse remitting MS (RRMS) patients. Materials and methods: Thirty-five RRMS patients (15 males and 20 females; median age 42 (20–55) years) and thirty-five age-sex matched healthy controls (13 males and 22 females; median age 37 (21–60) years) were included in this study. All patients were diagnosed with MS according to the criteria of McDonald. Results: IMA levels were significantly higher in RRMS patients (P < 0.001), while TAS and TOS did not show any significant difference between groups (P = 0.870 and P = 0.460, respectively). Conclusions: Our results suggest IMA as a more efficient serum marker than TAS and TOS in detecting the oxidative stress in MS patients. Serum oxidative stress markers should be included in future study protocols besides clinical and radiological parameters.

Ischemia Modified Albumin Levels and Oxidative Stress in Patients with Bladder Cancer

BACKGROUND Impaired oxidative/antioxidative status plays an important role in the pathogenesis of many diseases like cancer. The aim of this study was to evaluate the levels of the novel marker ischemia modified albumin (IMA) and albumin adjusted-IMA (Adj-IMA) in patients with bladder cancer (BC) as well as its association with total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI). MATERIALS AND METHODS Forty male patients with BC (mean age, 67.4±12 years) and forty age-sex matched healthy persons (mean age 56.0±1.7 years) were included in this study. Serum levels of IMA, TAS, TOS were analyzed and Adj- IMA and OSI was calculated. RESULTS Serum IMA, TOS and OSI values were significantly higher in patients with BC compared to controls (p<0.0001, p=0.01 and p=0.01, respectively), whereas TAS was significantly lower in BC patients (p=0.04). There was no significant difference for serum albumin-adjusted IMA levels between groups (p=0.4). CONCLUSIONS In this study, it was found that there was an impaired oxidative/antioxidant status in favor of oxidative stress in BC patients. This observation was not confirmed by Adj-IMA calculation. There is no published report about serum concentrations of IMA in patients with BC. Further studies are needed to establish the relationship of IMA and oxidative stress parameters in BC and the significance of IMA to other cancers.

No association between vitamin D levels and inflammation markers in patients with acute coronary syndrome

PURPOSE A modern concept regards acute coronary syndrome (ACS) as an auto-inflammatory disorder. The purpose of the present study is to assess the plasma levels of inflammation related to biomarkers and cytokines in ACS patients and to correlate the values with 25-hydroxy vitamin D3 (calcidiol). There are no previously published reports concerning serum concentrations of inflammatory markers in patients with hypovitaminosis D in ACS. PATIENTS AND METHODS Eighty-eight consecutive patients with ACS [n=47 ST elevation myocardial infarction (STEMI), n=41 unstable angina pectoris (USAP)] were enrolled within 12h after symptoms. The blood samples were collected on admission in order to evaluate calcidiol, serum amyloid A (SAA), interleukin (IL)-6, interleukin (IL)-10, tumor necrosis factor-alpha (TNFα) and high sensitivity C-reactive protein (hsCRP). RESULTS Calcidiol, TNFα and SAA levels were significantly lower (p=0.01, p<0.01 and p<0.01 respectively), whereas hsCRP levels were significantly higher (p<0.01) in STEMI group as compared to USAP group. In the STEMI group, there were negative correlations between SAA and hsCRP (r=-0.347; p=0.01) and SAA and IL-6 (r=-0.356; p=0.01). There was a positive correlation between IL-6 and hsCRP (r=0.529; p<0.01). In the USAP group, it was found that there were a strong negative correlation between SAA and hsCRP (r=-0.75; p<0.01) and a positive correlation between IL-6 and TNF-α (r=0.54; p<0.01). CONCLUSION This study demonstrates that calcidiol levels are not associated with the inflammation markers in patients with acute phase ACS.

Homocysteine, Paraoxonase-1 and Vascular Endothelial Dysfunction: Omnibus viis Romam Pervenitur

Increased oxidative stress, alterations of lipid metabolism and induction of thrombosis have been suggested to be pathogenic links which are present between hyperhomocysteinaemia and atherosclerosis. However, the mechanism by which homocysteine (Hcy) can promote atherogenesis is far from clear and it has been debated. In the presence of cardiovascular risk factors, endothelial dysfunction is the central commodity which converges a plenty of factors, which have been named as atherogenic. Now-a-days, there are only few studies which have presented the correlation between antioxidant enzyme HDL-associated-paraoxonase 1(PON1) and Hcy in atherosclerosis. Both PON 1 and Hcy have been implicated in human diseases which are related to endothelial dysfunction. Although paraoxonases have the ability to hydrolyze a variety of substrates, only one of them, Hcy-thiolactone, is known to occur naturally. It seems very likely that the involvement of Hcy in atherosclerotic disease is mediated through its interactions with PON1.

Impaired oxidative balance and association of blood glucose, insulin and HOMA-IR index in migraine

INTRODUCTION The nature of the relationship between glucose metabolism and occurrence of migraine has not been elucidated precisely. This study investigated the status of oxidative/antioxidative balance and its relationship with the glucose metabolism in migraineurs to get new points of view for the underlying oxidative mechanisms. MATERIALS AND METHODS Sixty migraineurs and 46 control subjects were included in the study. Oxidative stress index, total oxidant and antioxidant status of both groups were examined in addition to the insulin and HOMA-IR index levels. RESULTS HOMA-IR index was significantly enhanced in migraineurs (P = 0.038); similarly oxidative stress index and total oxidant status were higher in patients compared to the controls (P < 0.001 for both). CONCLUSION This preliminary study shows that oxidative/antioxidative balance shifts towards the oxidative status in migraine. Higher total oxidant status and elevated HOMA-IR index might play a role in the potential early pathogenesis for migraine.