The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis.

The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients' sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol-disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol-disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol-disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol-disulfide homeostasis in multiple sclerosis patients.

High-density lipoprotein dysfunction in carotid artery stenosis.

Background: High density lipoprotein (HDL) is well established to have an athero-protective role under normal conditions; however, pro-inflammatory alteration of HDL proteins may transform the HDL particle into a dysfunctional molecule. Our aim was to investigate HDL dysfunction by measuring enzyme-based markers in carotid artery stenosis (CAS). Patients and methods: All participants underwent duplex ultrasound and 52 subjects diagnosed with CAS and 51 subjects who had no significant stenosis (as controls) were enrolled in this study. Serum lipid profiles and serum parameters associated with dysfunctional HDL including myeloperoxidase (MPO), paraoxonase 1 (PON1), arylesterase (ARE) activity, and lipid hydroperoxide (LOOH) levels were measured. Results: It was found that the patients with CAS had increased levels of MPO and LOOH while PON1 activity was decreased. There was no significant difference between the CAS and non-CAS groups in terms of HDL levels. MPO/PON1, MPO/ARE, and LOOH/PON1 ratios were significantly increased in the CAS group. MPO/PON1 and MPO/ARE ratios both demonstrated significant correlations with degree of stenosis (%). Conclusions: The MPO/PON1 and MPO/ARE ratios may be potential serum markers that can enable the monitoring of HDL functionality and the assessment of atherosclerotic disease risks. Additionally, monitoring the oxidative balance of lipids on HDL molecules by LOOH/PON1 ratio may have value in the early detection of pro-atherosclerotic transformation of the HDL particle.

A commentary on the paper, 'Development and validation of a novel automatable assay for cholesterol efflux capacity'.

The determination of functionality or quality of high-density lipoproteins (HDL) is assuming a central stage in the prediction of cardiovascular diseases (CVD). To assess HDL quality, several attempts have been made to develop an automated, cost-effective cholesterol efflux capacity (CEC) system with few operational steps that might be used in clinical settings for large throughput testing. The work of Dr. Ohkawa and co-workers seems to address this issue and provide a solution for the same (Bioscience Reports (2023), 43 BSR20221519, https://doi.org/10.1042/BSR20221519). Earlier work from the author's lab utilized a radioisotope and cell-free CEC assay known as the immobilized liposome-bound gel beads (ILGs) method. However, this assay required a centrifugation step to separate the cells and was not suitable for automation. To overcome these limitations, two very important changes were made: (i) magnetic beads were used instead of gel beads that allowed them to avoid the centrifugation process that would allow ease of setting up an autonomous analyzer; (ii) porous magnetic beads were coated with liposomes containing fluorescently tagged cholesterol instead radiolabeled cholesterol. These two changes can be considered not only significant but also novel as they were highly suitable for CEC testing. The authors reported the successful development of a simple immobilized liposome-based magnetic beads (ILMs) automated system to measure CEC, which provided both consistent performance and satisfactory correlation with the other methods. Thus, we feel the present study will open newer avenues for measuring the quality of HDL in addition to the quantity of HDL-cholesterol in clinical settings in a more robust way.

Cardiovascular Disease in South Asian Immigrants: a Review of Dysfunctional HDL as a Potential Marker.

South Asians (SAs) account for a quarter of the world's population and are one of the fastest-growing immigrant groups in the United States (US). South Asian Immigrants (SAIs) are disproportionately more at risk of developing cardiovascular disease (CVD) than other ethnic/racial groups. Atherosclerosis is a chronic inflammatory disorder and is the major cause of CVD. Traditional CVD risk factors, though important, do not fully explain the elevated risk of CVD in SAIs. High-density lipoproteins (HDLs) are heterogeneous lipoproteins that modify their composition and functionality depending on physiological or pathological conditions. With its cholesterol efflux, anti-inflammatory, and antioxidant functions, HDL is traditionally considered a protective factor for CVD. However, its functions can be compromised under pathological conditions, such as chronic inflammation, making it dysfunctional (Dys-HDL). SAIs have a high prevalence of type 2 diabetes and metabolic syndrome, which may further promote Dys-HDL. This review explores the potential association between Dys-HDL and CVD in SAIs and presents current literature discussing the role of Dys-HDL in CVD.

Dynamic Resistance Exercise Alters Blood ApoA-I Levels, Inflammatory Markers, and Metabolic Syndrome Markers in Elderly Women.

Combined endurance and dynamic-resistance exercise has important anti-inflammatory effects, altering vascular endothelial function, and helping to prevent and treat aging-related metabolic syndrome (MS). We studied changes in 40 elderly women aged ≥ 65 years (control group (no MS), n = 20, mean age: 68.23 ± 2.56 years; MS group, n = 19, mean age: 71.42 ± 5.87 years; one left). The exercise program comprised dynamic-resistance training using elastic bands, three times weekly, for six months. We analyzed body composition, blood pressure, physical fitness, and MS-related blood variables including ApoA-I, antioxidant factors, and inflammatory markers. After the program, the MS group showed significant reductions in waist-hip ratio, waist circumference, diastolic blood pressure, blood insulin, and HOMA-IR, and a significant increase in HSP70 (p < 0.05). Both groups showed significant increases in ApoA-I levels, ApoA-I/HDL-C ratio, SOD2, IL-4, and IL-5 levels (p < 0.05). Active-resistance training-induced changes in ApoA-I were significantly positively correlated with changes in HDL-C and HSP70, and significantly negatively correlated with changes in triglycerides, C-reactive protein, and TNF-α (p < 0.05). Active-resistance training qualitatively altered HDL, mostly by altering ApoA-I levels, relieving vascular inflammation, and improving antioxidant function. This provides evidence that dynamic-resistance exercise can improve physical fitness and MS risk factors in elderly women.

Clinicoradiological evaluation of oxidative stress activity in acute cerebral infarction in the first 24 h and the qualitative importance of dysfunctional HDL in stroke.

BACKGROUND: Acute cerebral infarction (ACI) occurs as a result of instant disruption of vascular flow that causes disbalance between oxidative/antioxidative activity. We examined the relationship of serum neuro-oxidative stress parameters with stroke severity and infarct volume in ACI and emphasized the qualitative importance of high-density lipoprotein (HDL) on its relationship with myeloperoxidase (MPO) and paraoxonase-1 (PON1) in the acute period of stroke. METHODS: One hundred ACI patients applied within the first 24 h and 50 healthy volunteers were included. The patient group was evaluated with demographic data (including arrival serum biochemical assessment), clinical disability scores, infarct volume, serum oxidative/antioxidative parameters (lipid hydroperoxide (LOOH), MPO, PON1, MPO/PON ratio). The relevant serum parameters were compared with the control group. Dysfunctional HDL measurement was based on detecting dysfunctionality as a result of a high positive correlation between the dysfunctional feature of HDL and the MPO/PON ratio. The correlation of serum parameters, clinical disability score, and infarct volume were evaluated, and independent analyses of variability with comorbidities were performed. RESULTS: A negative correlation between PON1 and arrival NIH score/scale (NIHSS), LOOH and discharge modified rankin scale (mRS), triglyceride level, and infarct volume; a positive correlation between MPO\PON ratio and infarct volume was determined. Logistic regression analyses showed that hypertension, diabetes, and high HbA1C may be predictors of stroke severity, and diabetes mellitus, high HbA1C, infarct volume, and high NIHSS score may be predictors of early disability (p < 0.005). The ROC curve analysis revealed that determining the cut-off value for LOOH is of importance in determining early disability scores (7.2 and 6.2, respectively). DISCUSSION: The balance between oxidative and antioxidative stress parameters and their quantitative/qualitative changes is of importance, especially in the acute period of ACI. Dysfunctional HDL's evolution and its relationship with other oxidants are significant not only in the cardiovascular aspect but also in the clinicoradiological aspect.

MiR-223-3p levels in the plasma and atherosclerotic plaques are increased in aged patients with carotid artery stenosis; association with HDL-related proteins.

BACKGROUND: Cardiovascular diseases are still the main cause of death worldwide. Our aim was to analyse the link between miR-223-3p levels, dysfunctional HDL and the age of patients with carotid artery stenosis (CAS). METHODS AND RESULTS: Thirty-two CAS patients enrolled for endarterectomy were divided in 2 groups: aged over 65 years (n = 19) and under 65 years (n = 13). Plasma samples and atherosclerotic plaques from the carotid artery were collected from all patients. Plaque levels of miR-223-3p and its primary transcript (pri-miR-223) were assessed, together with Drosha, Dicer, apolipoprotein (apo)A-I, apoE and myeloperoxidase (MPO) gene expression. In the plasma and plaques, miR-223-3p expression levels were significantly increased in CAS patients over 65 years. Positive correlations between plaque miR-223-3p and pri-miR-223 levels with Drosha, apoA-I and MPO expression were observed. Significantly increased miR-223-3p levels in the plasma of CAS patients over 65 years were measured. Significant correlations between plasma miR-223-3p levels and HDL-related proteins were determined. The variance of plasma miR-223-3p levels was predicted significantly by the multiple regression models using either age, clinical variables, blood lipids or oxidative and inflammatory parameters. Receiver operator characteristic analysis revealed that plasma miR-223-3p levels and HDL-related proteins (MPO activity/apoA-I ratio, MPO specific activity) were correlated with advanced age. CONCLUSIONS: Taken together, these data suggest that plasma levels of miR-223-3p are independently associated with ageing in CAS patients and that, correlated with parameters associated with dysfunctional HDL, could predict the aggravation of CAS in elderly patients.

Is a High HDL-Cholesterol Level Always Beneficial?

The specific interest concerning HDL cholesterol (HDL-C) is related to its ability to uptake and return surplus cholesterol from peripheral tissues back to the liver and, therefore, to its role in the prevention of cardiovascular diseases, such as atherosclerosis and myocardial infarction, but also transient ischemic attack and stroke. Previous epidemiological studies have indicated that HDL-C concentration is inversely associated with the risk of cardiovascular disease and that it can be used for risk prediction. Some genetic disorders are characterized by markedly elevated levels of HDL-C; however, they do not translate into diminished cardiovascular risk. The search of the potential causative relationship between HDL-C and adverse events has shifted the attention of researchers towards the composition and function of the HDL molecule/subfractions. HDL possesses various cardioprotective properties. However, currently, it appears that higher HDL-C is not necessarily protective against cardiovascular disease, but it can even be harmful in extremely high quantities.

Excesive consumption of unsaturated fatty acids leads to oxidative and inflammatory instability in Wistar rats.

Lifestyle modifications such as increase in high-fat food consumption importantly increases the risks for cardiovascular disease. The principal objective of this study is to analyze effects of different high fat diet (HFD) sources on haemodynamic parameters, lipid and oxidative profile, myeloperoxidase activity, and markers of inflammation (IL-6/pentraxin-3). HFD containing 20% of fat, provided by lard (saturated) or soybean oil (unsaturated), as well as control diet were administering to three groups (L, SO and C). Food efficiency ratio and plasma lipids were significantly elevated in both HFD groups. However, only SO group showed an increase in systolic arterial pressure, oxidative stress index, myeloperoxidase activity, liver lipids as well as markers of inflammation: IL-6 and pentraxin-3 (PTX3). In summary, these results indicate inflammogenic potential of excessive soybean oil consumption in triggering liver damage.

Scavenger Receptor BI Induced by HDL From Coronary Heart Disease May Be Related to Atherosclerosis.

This study aims to determine whether dysfunctional High Density Lipoprotein (HDL) influenced the expression of scavenger receptor class B type Ⅰ (SR-B1) to determine reverse cholesterol transport. Blood samples obtained from coronary heart disease patients confirmed by angiography were collected. HDL was extracted from the blood via ultracentrifugation. Then, the HDL was injected into apoE-/- mice, and the HepG2 cells cultured with Dulbecco's modified eagle medium (DMEM) were added the HDL extracted from coronary heart disease patients. As controls, normal cases without coronary heart disease (CHD) and patients with angina pectoris and acute myocardial infarction were used. The protein expression levels of SR-B1 were detected by western blot, and the lipid accumulation levels were detected by Oil Red O staining in both tissues and cell levels. These results revealed that the HDL obtained from CHD patients downregulate the SR-B1 expression in ex vitro and in vitro studies. In addition, dysfunctional HDL may result in lower SR-B1 expression levels. The degree of SR-B1 expression levels could be relative to the degree of coronary congestion. Along with the increase in severe coronary congestion, such as myocardial infarction, the SR-B1 expression levels were lower. The dysfunctional HDL derived from coronary heart disease patients decreased the expression of SR-B1, and promoted lipid accumulation.

Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications.

High-density lipoproteins (HDLs) are a class of blood particles, principally involved in mediating reverse cholesterol transport from peripheral tissue to liver. Omics approaches have identified crucial mediators in the HDL proteomic and lipidomic profile, which are involved in distinct pleiotropic functions. Besides their role as cholesterol transporter, HDLs display anti-inflammatory, anti-apoptotic, anti-thrombotic, and anti-infection properties. Experimental and clinical studies have unveiled significant changes in both HDL serum amount and composition that lead to dysregulated host immune response and endothelial dysfunction in the course of sepsis. Most SARS-Coronavirus-2-infected patients admitted to the intensive care unit showed common features of sepsis disease, such as the overwhelmed systemic inflammatory response and the alterations in serum lipid profile. Despite relevant advances, episodes of mild to moderate acute kidney injury (AKI), occurring during systemic inflammatory diseases, are associated with long-term complications, and high risk of mortality. The multi-faceted relationship of kidney dysfunction with dyslipidemia and inflammation encourages to deepen the clarification of the mechanisms connecting these elements. This review analyzes the multifaced roles of HDL in inflammatory diseases, the renal involvement in lipid metabolism, and the novel potential HDL-based therapies.

HDL Dysfunctionality: Clinical Relevance of Quality Rather Than Quantity.

High-density lipoproteins (HDLs) represent a class of lipoproteins very heterogeneous in structure, composition, and biological functions, which carry out reverse cholesterol transport, antioxidant, anti-inflammatory, antithrombotic, and vasodilator actions. Despite the evidence suggesting a clear inverse relationship between HDL cholesterol (HDL-c) concentration and the risk for cardiovascular disease, plasma HDL cholesterol levels do not predict the functionality and composition of HDLs. The importance of defining both the amount of cholesterol transported and lipoprotein functionality has recently been highlighted. Indeed, different clinical conditions such as obesity, diabetes mellitus type 2 (T2DM), and cardiovascular disease (CVD) can alter the HDL functionality, converting normal HDLs into dysfunctional ones, undergoing structural changes, and exhibiting proinflammatory, pro-oxidant, prothrombotic, and proapoptotic properties. The aim of the current review is to summarize the actual knowledge concerning the physical-chemical alteration of HDLs related to their functions, which have been found to be relevant in several pathological conditions associated with systemic inflammation and oxidative stress.

High-Density Lipoprotein Modifications: A Pathological Consequence or Cause of Disease Progression?

High-density lipoprotein (HDL) is well-known for its cardioprotective effects, as it possesses anti-inflammatory, anti-oxidative, anti-thrombotic, and cytoprotective properties. Traditionally, studies and therapeutic approaches have focused on raising HDL cholesterol levels. Recently, it became evident that, not HDL cholesterol, but HDL composition and functionality, is probably a more fruitful target. In disorders, such as chronic kidney disease or cardiovascular diseases, it has been observed that HDL is modified and becomes dysfunctional. There are different modification that can occur, such as serum amyloid, an enrichment and oxidation, carbamylation, and glycation of key proteins. Additionally, the composition of HDL can be affected by changes to enzymes such as cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and phospholipid transfer protein (PLTP) or by modification to other important components. This review will highlight some main modifications to HDL and discuss whether these modifications are purely a consequential result of pathology or are actually involved in the pathology itself and have a causal role. Therefore, HDL composition may present a molecular target for the amelioration of certain diseases, but more information is needed to determine to what extent HDL modifications play a causal role in disease development.

Cholesterol Efflux Capacity and Cardiovascular Disease: The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

(1) Background and Aims: Efforts to reduce coronary artery disease (CAD) by raising high-density lipoprotein (HDL) cholesterol (HDL-C) have not been uniformly successful. A more important factor than HDL-C may be cellular cholesterol efflux mediated by HDL, which has been shown to be associated with CAD. In this report, we analyzed the influence of cardiovascular biomarkers and risk factors on cholesterol efflux in a prospective observational study of patients referred to coronary angiography. (2) Methods: HDL-mediated efflux capacity was determined for 2468 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who were referred to coronary angiography at baseline between 1997 and 2000. Median follow-up time was 9.9 years. Primary and secondary endpoints were cardiovascular and all-cause mortality, respectively. (3) Results: Cholesterol efflux strongly correlated with HDL-related markers including HDL cholesterol, HDL phospholipids, and apolipoproteins AI and AII, as well as HDL particle concentration, which was not seen for low density lipoprotein (LDL) markers including LDL cholesterol and apoB. Cholesterol efflux was associated negatively with C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), and serum amyloid A. Cardiovascular mortality was higher in patients in the lowest cholesterol efflux quartile. This association was weakened, but not fully abolished, after adjustment for HDL cholesterol. (4) Conclusions: We demonstrate that cholesterol efflux was associated with HDL-composition as well as inflammatory burden in patients referred for coronary angiography, and that this inversely predicts cardiovascular mortality independently of HDL cholesterol.

Pro-inflammatory HDL in women with obesity and nonalcoholic steatohepatitis.

BACKGROUND: Individuals with non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), are at increased risk for cardiovascular events, independent of traditional risk factors. Limited data on pro-inflammatory high density lipoprotein (HDL) in NASH exists in the literature. We hypothesized that HDL from individuals with NASH would be more pro-inflammatory than HDL from individuals without NASH. METHODS: Study participants were individuals with obesity who had undergone bariatric surgery with wedge liver biopsy. Using HDL isolated from serum obtained from study participants at the time of surgery, HDL-elicited macrophage cytokine expression (TNF-α, IL-1ß, and IL-6) from THP-1 macrophages, HDL-associated receptor expression (ABCA1 and ABCG1) from apolipoprotein E deficient (apo E-/-) mouse peritoneal macrophages, and isolevuglandin (isoLG) modified HDL were measured. RESULTS: 11 women with NASH and 15 women without NASH were included in the study. Both TNF-α (P = 0.032) and IL-1ß (P = 0.029) were significantly more expressed by THP-1 macrophages exposed to HDL from women with NASH compared to women without NASH. ABCA1 and ABCG1 expression by apo E-/- mouse peritoneal macrophages was not significantly different when exposed to HDL from either women with NASH or women without NASH. IsoLG-modified HDL isolated from the serum of women with NASH trended higher than women without NASH. CONCLUSION: Our study suggests a more pro-inflammatory HDL in women with obesity and NASH compared to women with obesity and without NASH.

Cardioprotective Properties of HDL: Structural and Functional Considerations.

BACKGROUND: As Mendelian Randomization (MR) studies showed no effect of variants altering HDL-cholesterol (HDL-C) levels concerning Cardiovascular Disease (CVD) and novel therapeutic interventions aiming to raise HDL-C resulted to futility, the usefulness of HDL-C is unclear. OBJECTIVE: As the role of HDL-C is currently doubtful, it is suggested that the atheroprotective functions of HDLs can be attributed to the number of HDL particles, and their characteristics including their lipid and protein components. Scientific interest has focused on HDL function and on the causes of rendering HDL particles dysfunctional, whereas the relevance of HDL subclasses with CVD remains controversial. METHODS: The present review discusses changes in quality as much as in quantity of HDL in pathological conditions and the connection between HDL particle concentration and cardiovascular disease and mortality. Emphasis is given to the recently available data concerning the cholesterol efflux capacity and the parameters that determine HDL functionality, as well as to recent investigations concerning the associations of HDL subclasses with cardiovascular mortality. RESULTS: MR studies or pharmacological interventions targeting HDL-C are not in favor of the hypothesis of HDL-C levels and the relationship with CVD. The search of biomarkers that relate with HDL functionality is needed. Similarly, HDL particle size and number exhibit controversial data in the context of CVD and further studies are needed. CONCLUSION: There is no room for the old concept of HDL as a silver bullet,as HDL-C cannot be considered a robust marker and does not reflect the importance of HDL particle size and number. Elucidation of the complex HDL system, as well as the finding of biomarkers, will allow the development of any HDL-targeted therapy.

Diabetes-induced Alterations in HDL Subfractions Distribution.

INTRODUCTION: Diabetes mellitus (DM) due to its increasing prevalence and associated morbidity and mortality has become a serious public health problem. In DM, HDL may lose its beneficial features and become proatherogenic due to its altered biological activity thus increasing cardiovascular risk. The aim of this study was to assess the influence of the presence of diabetes mellitus type 2 and its duration on the distribution of HDL subfractions. Moreover, the effect of statin treatment on HDL subfraction share was analysed in this study. METHODS: The study group consisted of 50 patients with newly diagnosed DM and 50 persons with DM for longer than 10 years while the control group consisted of 50 healthy volunteers. HDL subfractions were analysed with the use of Lipoprint. RESULTS: We demonstrated progressive worsening of heart functioning and impairment of its structure in the course of diabetes mellitus. Moreover, we observed that HDL-6 subfraction and intermediate HDL fraction are lowest in the group with advanced DMt2 compared to the group with newly diagnosed DM and a healthy control group. Finally, the results of our study indicated the effect of statin treatment on HDL subfractions that seems not to be advantageous. CONCLUSION: It seems that in patients with diabetes mellitus compromised antiatherogenic properties of HDL, as a result of oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein, increase cardiovascular risk.

Biological Consequences of Dysfunctional HDL.

Epidemiological studies have suggested an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular disease. HDLs promote reverse cholesterol transport (RCT) and possess several putative atheroprotective functions, associated to the anti-inflammatory, anti-thrombotic and anti-oxidant properties as well as to the ability to support endothelial physiology. The assumption that increasing HDL-C levels would be beneficial on cardiovascular disease (CVD), however, has been questioned as, in most clinical trials, HDL-C-raising therapies did not result in improved cardiovascular outcomes. These findings, together with the observations from Mendelian randomization studies showing that polymorphisms mainly or solely associated with increased HDL-C levels did not decrease the risk of myocardial infarction, shift the focus from HDL-C levels toward HDL functional properties. Indeed, HDL from atherosclerotic patients not only exhibit impaired atheroprotective functions but also acquire pro-atherogenic properties and are referred to as "dysfunctional" HDL; this occurs even in the presence of normal or elevated HDL-C levels. Pharmacological approaches aimed at restoring HDL functions may therefore impact more significantly on CVD outcome than drugs used so far to increase HDL-C levels. The aim of this review is to discuss the pathological conditions leading to the formation of dysfunctional HDL and their role in atherosclerosis and beyond.

High-density lipoprotein (HDL) cholesterol - more complicated than we think?

INTRODUCTION AND OBJECTIVE: There are some clinical situations where a high level of HDL cholesterol (HDL-C) may be unfavourable. In these situations, HDL-C may undergo some changes, and even if its quantity is within the reference range, its quality is no longer the same. BRIEF DESCRIPTION OF STATE OF KNOWLEDGE: Diabetes is the state of elevated oxidative stress. Studies conducted to-date have revealed an increased production of the reactive forms of oxygen as the result of tissue damage in diabetes patients. The expression 'dysfunctional HDL' has been coined in the literature to describe high-density lipoproteins that lose their antioxidative and anti-inflammatory properties, that is, HDL-C that loses its basic functions. Recent observational studies have confirmed that the atheroprotective activity of properly functioning HDL-C is frequently impaired in clinical situations associated with oxidative stress. The presented review lays the foundation for a new approach to understanding how the functional properties of HDL help reduce cardiovascular risk. CONCLUSIONS: In the light of presented findings it seems that there is a need to seek a better diagnostic marker than HDL-C level. This study presents some possible directions for future research to bring us closer to the full understanding of the HDL particle and its role in patients with ischemic heart disease and type 2 diabetes.

Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions?

INTRODUCTION: Many lines of evidence indicate that low levels of HDL cholesterol increase the risk of cardiovascular disease (CVD). However, recent clinical studies of statin-treated subjects with established atherosclerosis cast doubt on the hypothesis that elevating HDL cholesterol levels reduces CVD risk. Areas covered: It is critical to identify new HDL metrics that capture HDL's proposed cardioprotective effects. One promising approach is quantitative MS/MS-based HDL proteomics. This article focuses on recent studies of the feasibility and challenges of using this strategy in translational studies. It also discusses how lipid-lowering therapy and renal disease alter HDL's functions and proteome, and how HDL might serve as a platform for binding proteins with specific functional properties. Expert commentary: It is clear that HDL has a diverse protein cargo and that its functions extend well beyond its classic role in lipid transport and reverse cholesterol transport. MS/MS analysis has demonstrated that HDL might contain >80 different proteins. Key challenges are demonstrating that these proteins truly associate with HDL, are functionally important, and that MS-based HDL proteomics can reproducibly detect biomarkers in translational studies of disease risk.