High-density Lipoprotein Cholesterol Function Research Articles

Assessing High-Density Lipoprotein: Shifting Focus from Quantity to Quality in Cardiovascular Disease Risk Assessment

High-density lipoprotein cholesterol (HDL) has long been regarded as a protective factor against cardiovascular disease (CVD). However, recent research challenges this notion, suggesting that HDL functionality rather than its quantity may be a more accurate predictor of CVD risk. While epidemiological studies have traditionally found that higher HDL levels are associated with reduced CVD risk, intervention trials aiming to elevate HDL levels have yielded inconsistent results. Moreover, observational studies have reported that unusually high HDL levels are associated with increased mortality rates. These discrepancies underscore the complexity of the role of HDL in CVD. Reverse cholesterol transport, facilitated by HDL, plays a crucial role in preventing atherosclerosis by removing cholesterol from peripheral tissues. Additionally, HDL exhibits anti-inflammatory properties by inhibiting endothelial adhesion molecules and suppressing pro-inflammatory cytokines. Recent studies have highlighted the importance of HDL particle number, size, and functionality in assessing CVD risk. For instance, increased HDL particle number and larger particle size have been associated with reduced CVD risk, independent of HDL cholesterol levels. Furthermore, HDL’s cholesterol efflux capacity has emerged as a promising biomarker for predicting CVD risk, with higher efflux capacity correlating with lower CVD incidence and mortality. This article reviews the latest findings regarding the role of HDL in CVD risk assessment, emphasizing the need to focus on HDL quantity and HDL quality.

Serum Isthmin-1 is negatively correlated with HDL-C in type 2 diabetes mellitus

BackgroundIsthmin-1 (Ism-1) is a newly identified insulin-like adipokine that increases glucose uptake by adipocytes and inhibits hepatic lipid synthesis. Recent studies have shown that Ism-1 can improve the metabolic disorders associated with type 2 diabetes mellitus (T2DM) and improve lipid metabolism. The classic function of high-density lipoprotein cholesterol (HDL-C) is to transport cholesterol from extra-hepatic tissues to the liver for metabolism. In contrast, disorders of lipid metabolism and inflammation are the leading causes of atherosclerosis (As). Atherosclerosis often manifests as loss of elasticity, lipid accumulation, fibrous tissue proliferation and calcium deposits in the affected arteries, eventually forming plaques. AimTo illustrate the correlation between HDL-C and Ism-1 in T2DM, and the relationship between lipoprotein cholesterol and carotid plaque. MethodsA total of 128 patients with T2DM were enrolled in the study and basic information was collected. HDL-C levels were measured chemically. Serum Ism-1 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Linear regression analysis was used to assess the correlation between serum Ism-1 levels and HDL-C in patients with T2DM. Basic information was again collected from 226 patients with T2DM. Independent sample t-tests were performed to explore the relationship between carotid plaque formation and lipids. ResultsHDL-C was divided into four groups according to quartiles and there was a between-group difference in Ism-1 (p = 0.040). Multivariable linear regression showed a negative association between Ism-1 and HDL-C in T2DM (β = −0.235, p < 0.001), even after adjusting for related factors (β = −0.165, p = 0.009). Low-density lipoprotein cholesterol (LDL-C) and HDL-C showed significant differences between the carotid plaque group and the non-carotid plaque group (pLDL-C = 0.007, pHDL-C = 0.003). ConclusionSerum Ism-1 and HDL-C are negatively correlated in T2DM. LDL-C is significantly higher in carotid plaque group than non-carotid plaque group, while HDL-C is significantly lower than in the non-carotid plaque group.

Role of high-density lipoprotein cholesterol in health and diseases

Primary function of high-density lipoprotein cholesterol is to reverse transport the cholesterol from extrahepatic cell to liver for its metabolism and excretion. Studies have demonstrated the anti-inflammatory, anti-atherogenic, anti-oxidant, and anti-diabetic property of the high-density lipoprotein cholesterol. Although the exact mechanism still remains unelucidated, high-density lipoprotein cholesterol is a complex of lipids and proteins carrying many associated cargo molecules such as enzymes, signaling molecules, miRNA, which imparts overall functionality of high-density lipoprotein cholesterol for its beneficial health effects. However, the protein and lipids components get transform by the enzymes associated with high-density lipoprotein cholesterol, hyperglycemia, oxidative stressor, and free radicals, leading to qualitative and quantitative alterations in high-density lipoprotein cholesterol (HDLc) and diminishes its beneficial effects. In this review, we have discussed the different property of high-density lipoprotein cholesterol, its function and factors influencing HDLc property in light of anti-inflammatory activity in rheumatoid arthritis and the role of cholesterol-lowering statin drug in enhancing the beneficial effect of high-density lipoprotein cholesterol in different cell types.

High-density lipoprotein-cholesterol functionality and metabolic syndrome: Protocol for review and meta-analysis.

Introduction:The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia and an increased risk of cardiovascular events. One function of high-density lipoprotein (HDL) cholesterol (HDL-C) is the cholesterol-efflux pathway, which is the pathway where cholesterol is removed from macrophages within the arterial walls back into the bloodstream and out to the liver. As one of the key functions of HDL, their hypothesis was that if they could measure HDL-C-efflux capacity, they would have a better handle on the role of HDL in atherosclerosis. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between HDL-C functionality and MetS. The aim of this study is to examine this association of HDL-C functionality with MetS in different ages and sex.Methods and analysis:The update systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (i.e., PubMed, EMBASE, Web of Science, and Google Scholar). Studies that examined the association between HDL-C functionality and MetS; focused on cohort, case-control, and cross-sectional studies; were conducted among in adults aged 40 to 70 years; provided sufficient data for calculating odds ratio or relative risk with a 95% confidence interval; were published as original articles written in English or other languages; and have been published until January 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators.Ethics and dissemination:Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal.Trial registration number: PROSPERO (CRD42018083465).

The clinical relevance of dysfunctional HDL in patients with coronary artery disease: A 3-year follow-up study

The well known atheroprotective effects of high density lipoprotein cholesterol (HDL) are based on reverse cholesterol transport as well as anti-inflammatory properties [1,2]. Primary prevention studies have confirmed that HDL levels are strongly associated with reduced cardiovascular events [3]. However, recent evidence supports the notion that HDL functionality may be impaired under certain conditions [4,5]. Ansell and colleagues reported that HDL isolated from subjects with coronary artery disease (CAD) had less antiinflammatory activity than HDL derived from healthy controls, thus providing the first evidence that HDL may be dysfunctional in this setting [6]. Interestingly, in CAD patients HDL has shown to be even proinflammatory, thus increasing monocyte chemiotaxis, reactive oxygen species production, endothelial dysfunction and cellular apoptosis [6,7]. Hence, HDL may not be protective in secondary prevention of coronary artery disease. This issue needs to be rapidly clarified since therapies that raise HDL levels are being investigated for the treatment of CAD patients [8,9]. In the present study we sought to determine whether higher HDL levels maintain their protective effects also in patients with CAD. From March 2006 to April 2009 we consecutively enrolled 184 patients with a first manifestation of CAD (mean age 62±10 years, male/female ratio 3:1). All patients taking lipid-lowering agents or other cardiovascular medications at admission were excluded from the study. Moreover, patients with relevant comorbidities (renal failure, COPD, infective or inflammatory diseases, autoimmune disorders, cancer) were also not considered. All subjects underwent coronary angiography and routine blood chemistry including high sensitivity C-reactive protein (hs-CRP) and lipid profile comprehensive of ApoB-100 and ApoA1 determination. The study was approved by our Institute Committee and all patients signed an informed consent. The study population was divided into groups with higher (N50 for women, N40 formen) and lower HDL levels (≤50 for women, ≤40 for men, Table 1), according to ATPIII criteria [10]. Groups did not significantly differ for demographic and antropometric characteristics as well as for the prevalence of cardiovascular risk factors and left ventricular ejection fraction (EF). Serum creatinine, fasting plasma glucose, uric acid and Pro-BNP were similar in the two groups. HDL and ApoA1 were significantly different but the groups did not differ with regard to LDL and ApoB-100 levels (Table 1). Patients with high HDL had significantly lower triglycerides and hs-CRP values (Table 1). Notably, statin treatment and dose were similar between the two groups (Table 2). Cardiovascular end-points were assessed by clinic visits and programmed phone contacts up to 3 years after the first admission. Determinations of lipid fractions were performed both at baseline and follow-up. No significant changes in HDL levels were observed during follow-up either in patients with high or low HDL (Fig. 1A,B). Major adverse cardiovascular events (MACE) consisted of: (1) mortality for all causes; (2) myocardial infarction (MI); (3) revascularization by percutaneous coronary intervention or by-pass surgery; (4) cerebrovascular events including transient ischemic attack and stroke. Data analysis was performed with SPSS 13.0 software package (SPSS Inc., Chicago). Numerical data are reported as

High-Density Lipoprotein-Mediated Anti-Atherosclerotic and Endothelial-Protective Effects: A Potential Novel Therapeutic Target in Cardiovascular Disease

Reduced levels of high-density lipoprotein cholesterol (HDL) are associated with a substantially increased risk of coronary disease and cardiovascular events. Furthermore, numerous studies have suggested that HDL may exert several potentially important antiatherosclerotic and endothelial-protective effects. In particular, the promotion of reverse cholesterol transport, i.e. cholesterol efflux from lipid-loaded macrophages in atherosclerotic lesions and the subsequent cholesterol transport back to the liver, has been proposed as an anti-atherogenic effect of HDL that may promote regression of atherosclerotic lesions. Moreover, endothelial dysfunction is thought to play a critical role in development and progression of atherosclerosis and several recent studies have suggested that HDL exerts direct endothelial-protective effects, such as stimulation of endothelial production of the anti-atherogenic molecule nitric oxide, anti-oxidant, anti-inflammatory and anti-thrombotic effects. Furthermore, it has been observed that HDL may stimulate endothelial repair processes, involving mobilisation and promotion of endothelial repair capacity of endothelial progenitor cells. The relative significance of these different potential anti-atherosclerotic effects of HDL remains still unclear at present. Importantly, at the same time it has been recognized that the vascular effects of HDL may be variable, i.e. the capacity of HDL to stimulate macrophage cholesterol efflux and endothelial-protective effects may be altered in patients with inflammatory or cardiovascular disease. The further characterisation of underlying mechanisms and the identification of the clinical relevance of this "HDL dysfunction" are currently an active field of research. HDL-targeted treatment strategies are at present intensely evaluated and may lead to increased HDL plasma levels and/or HDL-stimulated anti-atherosclerotic effects. The cardiovascular protection provided by such approaches may likely depend on HDL function or quality, i.e. the anti-atherosclerotic and endothelial-protective properties of the on-treatment HDL. Currently, several HDL-raising treatment strategies are examined in clinical trials, i.e. extended-release niacin, the CETP inhibitors dalcetrapib and anacetrapib, reconstituted forms of HDL (i.e. CSL-111) or apoA-I mimetics, and some of these are already in large clinical outcome studies on top of statin therapy to determine their efficacy and safety for cardiovascular prevention.

Regulation of high‐density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease

Coronary artery disease is a primary co-morbidity in metabolic diseases such as metabolic syndrome, diabetes and obesity. One contributing risk factor for coronary artery disease is low high-density lipoprotein-cholesterol (HDLc). Several factors influence steady-state HDLc levels, including diet, genetics and environment. Perhaps more important to coronary artery disease is factors that attribute to the dynamics of reverse cholesterol transport, storage, and excretion of excess cholesterol. HDLc biogenesis, clearance and innate ability to serve as a cholesterol acceptor and transporter all contribute to HDLc's function as a negative regulator of cardiovascular disease. With the recent failure of torcetrapid, focus is being placed on HDLc biology and its role in various metabolic diseases. Low HDLc levels are often associated with an increased state of background inflammation. Recently, several syndromes with clear pro-inflammatory components have been shown to be inversely correlated with low HDLc levels in the absence of obesity, diabetes and metabolic syndrome. Early studies with HDLc during the acute-phase response suggest that HDLc is substantially physically modified during acute infection and sepsis, and recent studies show that HDLc is physically modified by chronic pro-inflammatory disease. In this review, several of these connections are described and cytokine signalling related to HDLc is examined.

HDL Cholesterol: Physiology, Pathophysiology, and Management

Numerous epidemiological studies have identified high-density lipoprotein cholesterol (HDL) to be an independent risk factor for coronary heart disease (CHD). HDL is an emerging therapeutic target that could rival the impact of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) on LDL and CHD risk reduction. HDL metabolism, HDL kinetics, the concentration of various HDL subclasses, and other genetic factors affecting HDL functionality may all contribute to the anti-atherogenic properties of HDL; thus, standard plasma measurement may not capture the full range of HDL effects. Algorithms have been suggested to treat low HDL levels in subgroups of patients; however, no formal HDL target goals or treatment guidelines have been implemented as there is a lack of strong clinical evidence to support effective pharmacologic therapy for primary risk reduction. Available therapies have a modest impact on serum HDL levels; however, emerging therapies could have a more significant influence.