Elevated High-density Lipoprotein Cholesterol Levels Research Articles

Clinical Effectiveness of Dienogest in the Treatment of Endometriosis

Objective: This paper aims to investigate the efficacy of desogestrel in the treatment of endometriosis. Methods: In this study, 61 patients with endometriosis in our hospital from January 2023 to December 2023 were selected and divided using the random sampling method. All the patients were treated with desogestrel and the pain symptom scores and HDL-C (high-density lipoprotein cholesterol) levels of the patients were compared before and after the treatment. The treatment effects and adverse effects during the administration of the drug were closely observed. Results: After the patients were treated with desogestrel, the effective rate of treatment was as high as 98.36%, and the incidence of adverse reactions during treatment was 6.55%. Compared with the pre-treatment period, the scores of various pain symptoms were significantly reduced and the HDL-C level was improved after treatment, with P < 0.05. Conclusion: Desogestrel showed significant efficacy in the treatment of endometriosis, effectively relieving patients’ pain while elevating HDL-C levels. In addition, the incidence of adverse reactions to this drug is relatively low, which is worth utilizing.

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.

Confounding association between plasma HDL-C levels and increased fracture risk: A correspondence.

This article explores the association between fractures, particularly in the elderly, and elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. The study challenges the conventional idea of HDL-C as "good cholesterol" by revealing its potential role as a risk factor for fractures. Factors contributing to fractures in the elderly, such as diminishing bone strength due to aging-related tissue breakdown, are discussed. Sedentary lifestyles, low bone mineral density (BMD), and habits like smoking and alcohol consumption compound fracture susceptibility. The study delves into mechanisms linking elevated HDL-C to fractures, using data from the ASPREE-Fracturesub-study of the ASPREE trial involving Australian and American participants aged 65 and above. The study showed that over a 4-year period, elevated HDL-C levels in healthy older people were linked to a 14% higher fracture risk. This revelation expands the understanding of fracture risk factors beyond the established norms. The article emphasizes the need to reconsider HDL-C's traditional role as an indicator of cardiovascular health, particularly in light of medications like Statins and Anacetrapib that raise HDL-C levels. It calls for further exploration into the relationship between HDL-C, fractures at varying sites, and different age groups. Practical implications involve incorporating fracture risk associated with high HDL-C into clinical considerations, alongside advocating lifestyle changes for optimal HDL-C levels. In summary, this study prompts a reevaluation of HDL-C's implications in clinical practice, demanding further investigation into the intricacies of this relationship.

#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD

Abstract Background and Aims Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels. Method Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality. Results Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C <1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders. Conclusion This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.

Interaction of periodontal clinical indicators in metabolic syndrome and nonalcoholic fatty liver disease: Implications for preventive interventions

IntroductionThe behavior of periodontal clinical indicators in metabolic syndrome (MetS) and fatty liver disease (NAFLD) are not clearly defined. It’s even considered that high-risk cases for NAFLD are currently underreported or not identified in a timely manner. The aim of the study is to elucidate the interaction of periodontal clinical indicators in MetS and NAFLD. Materials and methods: 336 patients were eligible because they met the diagnostic criteria for metabolic syn-drome and nonalcoholic fatty liver disease. Those selected were randomly selected for a cross-sectional study. Metabolic status and non-alcoholic fatty liver disease were measured using the MetS Metabolic Syndrome Diagnostic Criteria (NCEP/ATP-III) and laboratory tests, respectively. In addition, periodontal clinical indicators were evaluated: probing depth, clinical attachment, plaque index and gingival bleeding. ResultsThe association for NAFLD and probing depth was p = 0.736. The association for MetS and probing depth was p = 0.598. For NAFLD and clinical attachment loss, the association was p = 0.751. For MetS and clinical attachment loss, the association was p = 0.435. The plaque index for MetS was p = 0.238. The plaque index for NAFLD was p = 0.269. The gingival bleeding association for NAFLD was p = 0.673 and for MetS was p = 0.522. ConclusionsPeriodontal clinical indicators of metabolic syndrome were as-sociated with elevated serum levels of low-density lipoproteins (LDL), HDL-cholesterol, and triglycerides. However, when comparing the values in NAFLD and MetS, a greater significance is evident in the first study group.

Assessing the Benefits of Lifestyle Influences on Cardiovascu-lar Health After Acute Coronary Syndrome

Abstract: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Materials and methods: The study comprised two groups: group A (102 patients) that consumed 10 grams of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) which adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results: Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, were associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, acute myocardial infarction (AMI) recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of ejection fraction (EF) im-provement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions: In conclusion, our study emphasizes the potential benefits of com-bining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

Effect of sacubitril/valsartan on lipid metabolism in patients with chronic kidney disease combined with chronic heart failure: a retrospective study

Background and objectiveDyslipidemia is significantly more common in those with concurrent chronic kidney disease (CKD) and chronic heart failure (CHF). Sacubitril/valsartan has showcased its influence on both cardiac and renal functions, extending its influence to the modulation of lipid metabolism pathways. This study aimed to examine how sacubitril/valsartan affects lipid metabolism within the context of CKD and CHF.MethodsThis study adopted a retrospective design, focusing on a single center and involving participants who were subjected to treatment with sacubitril/valsartan and valsartan. The investigation assessed the treatment duration, with a particular emphasis on recording blood lipid indicators, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB). Furthermore, cardiac and renal functions, blood pressure, potassium levels, and other factors influencing the blood lipids were analyzed in both groups at identical time points.ResultsAfter 16 weeks of observation, the sacubitril/valsartan group exhibited lower TG levels compared to the valsartan group. Noteworthy was the fact that individuals undergoing sacubitril/valsartan treatment experienced an average reduction of 0.84 mmol/L in TG levels, in stark contrast to the valsartan group, which registered a decline of 0.27 mmol/L (P < 0.001). The sacubitril/valsartan group exhibited elevated levels of HDL-C and ApoA in comparison to the valsartan group (PHDL-C = 0.023, PApoA = 0.030). While TC, LDL-C, and ApoB decreased compared to baseline, the differences between groups were not statistical significance. Regarding cardiac indicators, there was an observed enhancement in the left ventricular ejection fraction (LVEF) within the sacubitril/valsartan group when compared to the baseline, and it was noticeably higher than that of the valsartan group. Spearman correlation analysis and multiple linear regression analysis revealed that medication, body mass index(BMI), and hemoglobin A1c (HbA1c) had a direct influencing effect on TG levels.ConclusionSacubitril/valsartan demonstrated improvements in lipid metabolism and cardiac indicators in patients with CKD and CHF. Specifically, it presented promising benefits in reducing TG levels. In addition, both BMI and HbA1c emerged as influential factors contributing to alterations in TG levels, independent of the administration of sacubitril/valsartan.

Reevaluating elevated HDL cholesterol levels in healthy older persons as a risk factor for various disease states

Reevaluating elevated HDL cholesterol levels in healthy older persons as a risk factor for various disease states

Knockdown of ADAMDEC1 ameliorates ox-LDL-induced endothelial cell injury and atherosclerosis progression.

This study was designed to investigate the role of a disintegrin and metalloproteinase domain-like protein decysin 1 (ADAMDEC-1) in atherosclerosis (AS). The Gene Expression Omnibus (GEO) database was utilized to identify differentially expressed genes (DEGs) between carotid atheroma plaque and carotid tissue adjacent atheroma plaque obtained from AS patients. Gene functional enrichment analysis was conducted on DEGs using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). QRT-PCR was employed to quantify mRNAs expression. AS animal model was established using ApoE-/- mice; serum triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were detected. Aortic sinus atherosclerotic lesions were observed using H&E staining and Oil Red O staining. ADAMDEC-1 was silenced using small interfering RNAs (siRNAs) in human vascular smooth muscle cells (HVSMCs). Cell proliferation, migration, and cell cycle progression were detected by cell count kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EDU), wound scratch healing assay, transwell assay, and flow cytometry, respectively. Western blot was used to evaluate various protein expression levels. Our results showed that ADAMDEC-1 was highly expressed in the serum of AS patients, consistent with the in silico results. The elevated TG, LDL-C, and HDL-C levels along with H&E and Oil Red O staining confirmed the successful establishment of the AS mouse model. ADAMDEC-1 expression was also elevated in AS mice. ADAMDEC-1 knockdown in HVSMCs suppressed cell proliferation, inhibited the expression of proliferating cell nuclear antigen (PCNA), and reduced the levels of matrix metalloproteinases (MMP2 and MMP9) proteins. Protein-protein interaction (PPI) analysis indicated that ADAMDEC-1 was associated with CXCL9, CCR5, TNF-α, TNFR1, and NF-κB-p50. The expression levels of CXCL9, CCR5, TNF-α, TNFR1, and NF-κB-p50 increased, while ADAMDEC-1 knockdown attenuated the expression of these proteins. Our study findings substantiate that ADAMDEC-1 may represent a novel target for AS.

Variants in the CETP gene affect levels of HDL cholesterol by reducing the amount, and not the specific lipid transfer activity, of secreted CETP.

Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters in plasma from high density lipoprotein (HDL) to very low density lipoprotein and low density lipoprotein. Loss-of-function variants in the CETP gene cause elevated levels of HDL cholesterol. In this study, we have determined the functional consequences of 24 missense variants in the CETP gene. The 24 missense variants studied were the ones reported in the Human Gene Mutation Database and in the literature to affect HDL cholesterol levels, as well as two novel variants identified at the Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital in subjects with hyperalphalipoproteinemia. HEK293 cells were transiently transfected with mutant CETP plasmids. The amounts of CETP protein in lysates and media were determined by Western blot analysis, and the lipid transfer activities of the CETP variants were determined by a fluorescence-based assay. Four of the CETP variants were not secreted. Five of the variants were secreted less than 15% compared to the WT-CETP, while the other 15 variants were secreted in varying amounts. There was a linear relationship between the levels of secreted protein and the lipid transfer activities (r = 0.96, p<0.001). Thus, the secreted variants had similar specific lipid transfer activities. The effect of the 24 missense variants in the CETP gene on the lipid transfer activity was mediated predominantly by their impact on the secretion of the CETP protein. The four variants that prevented CETP secretion cause autosomal dominant hyperalphalipoproteinemia. The five variants that markedly reduced secretion of the respective variants cause mild hyperalphalipoproteinemia. The majority of the remaining 15 variants had minor effects on the secretion of CETP, and are considered neutral genetic variants.

Sustenance Trial to Analyze the Effects of Black Soldier Fly Larvae Meal on the Reproductive Efficiency of Sows and the Hematological Properties of Suckling and Weaning Piglets.

The escalating demand for meat, driven by global population growth, necessitates sustainable solutions for animal feed production. This study investigated the effects of substituting conventional protein resources in sow and piglet dietary regimens with black soldier fly (BSF; Hermetia illucens) meal on reproductive efficiency, blood profile, piglet growth, and intestinal tissue morphology. The results indicate that substituting animal-derived and soy proteins with BSF meal does not compromise sow reproductive performance. Although no notable disparities were observed in piglet growth, the feed conversion ratio from the 28- to 35-day age marks were lower in the BSF-fed groups. This suggests that the animal protein-BSF substitution rate may require optimization, potentially involving chitin removal from BSF meal to enhance digestibility. Minor variations in the hematological composition and properties in piglets, with elevated high-density lipoprotein cholesterol levels in the high BSF group at the 28-day mark, were potentially attributable to the unique fatty acid composition of BSF meal. Moreover, this study potentiates future exploration into the efficacy of complete animal protein substitution with BSF meals on piglet nutrition and physiology, particularly in fattening pigs. The practical implementation of BSF meals in animal feed production holds promise for enhancing the sustainability of the swine industry.

Causal associations between blood lipids and brain structures: a Mendelian randomization study.

The potential causal association between dyslipidemia and brain structures remains unclear. Therefore, this study aimed to investigate whether circulating lipids are causally associated with brain structure alterations using Mendelian randomization analysis. Genome-wide association study summary statistics of blood lipids and brain structures were obtained from publicly available databases. Inverse-variance weighted method was used as the primary method to assess causality. In addition, four additional Mendelian randomization methods (MR-Egger, weighted median, simple mode, and weighted mode) were applied to supplement inverse-variance weighted. Furthermore, Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were performed for sensitivity analyses. After Bonferroni corrections, two causal associations were finally identified: elevated non-high-density lipoprotein cholesterol level leads to higher average cortical thickness (β = 0.0066mm, 95% confidence interval: 0.0045-0.0087mm, P = 0.001); and elevated high-density lipoprotein cholesterol level leads to higher inferior temporal surface area (β = 18.6077mm2, 95% confidence interval: 11.9835-25.2320mm2, P = 0.005). Four additional Mendelian randomization methods indicated parallel results. Sensitivity tests demonstrated the stability. Overall, the present study showed causal relationships between several lipid profiles and specific brain structures, providing new insights into the link between dyslipidemia and neurological disorders.

Causality of Diabetic Nephropathy and Age-Related Macular Degeneration: A Mendelian Randomization Study

PurposeAge-related macular degeneration (AMD) currently stands as the leading cause of irreversible vision loss in the present era. The primary objective of this study was to investigate the causal relationships between diabetic nephropathy (DN), its associated risk factors, and AMD among participants of European descent. MethodsGenetic variants associated with DN and its risk factors, encompassing glycemic traits, lipidemic traits, systolic/diastolic blood pressure, obesity, and urate, were obtained from previously published genome-wide association studies. Summary-level statistics for AMD were acquired from the FinnGen database. Univariable and multivariable Mendelian randomization (MR) were employed to conduct this investigation. ResultsOur MR analyses indicated that per 1-standard deviation (SD) increase of DN heightened the risk of overall AMD (p = 1.03 × 10–8, OR = 1.24). And these findings remained consistent when examining both dry AMD (p = 2.27 × 10–4, OR = 1.17) and wet AMD (p = 5.15 × 10–6, OR = 1.33). Additionally, there was a causal association between high-density lipoprotein-cholesterol (HDL-C) levels and an increased risk of AMD (p = 2.69 × 10−3, OR = 1.23), while triglycerides were found to mitigate the risk (p = 0.02, OR = 0.83). Notably, no significant associations were observed between other risk factors of DN and AMD. ConclusionsThese findings suggest that the impact of DN on the development of AMD may be more substantial than previously believed. Furthermore, elevated HDL-C levels appear to heighten the risk of AMD, whereas triglycerides may provide a protective effect.

CHARACTERISTICS OF DYSLIPIDEMIA IN THE CROATIAN RURAL AREA DAMAGED BY AN EARTHQUAKE. “THE SILENT KILLER HUNT” - CROATIAN SOCIETY OF HYPERTENSION PROJECT

Objective: Dyslipidemia is one of the most prevalent cardiovascular risk factors, making its detection and control essential due to the risk of serious complications. Prevention and sensible management of dyslipidemia can markedly alter cardiovascular morbidity and mortality. This study aimed to determine the prevalence of dyslipidemia among the adult population in a rural part of Croatia seriously damaged by the earthquake and evaluate the gender-associated differences in lipid profiles. Design and method: Blood samples of 244 subjects (188 women) (opportunistic screening) were collected under fasting conditions. The bloodwork results were analyzed using descriptive statistics and t-tests were used for checking differences between the sexes. Results: The average age of the whole group was 61.9 ± 14.3 years. Prevalence of hypercholesterolemia, hypertriglyceridemia, elevated LDL cholesterol levels and low HDL cholesterol levels were 59.0%, 34.8%, 57.0%, and 32.0%, respectively. Average values of total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol were 5.4 ± 1.7mmol/l, triglyceride 1.8 ± 1.1 mmol/l, 1.4 ± 0.3 mmol/l, and 3.3 ± 1.02 mmol/l. We failed to find a significant difference in total cholesterol and LDL cholesterol between men and women (p&gt;0.05). There was a statistically significant difference in triglyceride and HDL cholesterol levels between men and women with men showing higher levels of triglycerides (t = 2.08, p&lt;0.05) and lower levels of HDL cholesterol (t = -4.1, p&lt;0.05) than women. Conclusions: The prevalence of dyslipidemia in this rural area is high, higher than in other rural parts of Croatia indicating that stressful life after the earthquake and an unhealthy diet might contribute to this. Primary prevention i.e. education and regular examination of this vulnerable population should be in focus and even more intensive than in other rural, remote areas.

Coronary Artery Disease with Elevated Levels of HDL Cholesterol Is Associated with Distinct Lipid Signatures.

Levels of high-density lipoprotein cholesterol (HDL-C) are inversely associated with the incidence of coronary artery disease (CAD). However, the underlying mechanism of CAD in the context of elevated HDL-C levels is unclear. Our study aimed to explore the lipid signatures in patients with CAD and elevated HDL-C levels and to identify potential diagnostic biomarkers for these conditions. We measured the plasma lipidomes of forty participants with elevated HDL-C levels (men with >50 mg/dL and women with >60 mg/dL), with or without CAD, using liquid chromatography-tandem mass spectrometry. We analyzed four hundred fifty-eight lipid species and identified an altered lipidomic profile in subjects with CAD and high HDL-C levels. In addition, we identified eighteen distinct lipid species, including eight sphingolipids and ten glycerophospholipids; all of these, except sphingosine-1-phosphate (d20:1), were higher in the CAD group. Pathways for sphingolipid and glycerophospholipid metabolism were the most significantly altered. Moreover, our data led to a diagnostic model with an area under the curve of 0.935, in which monosialo-dihexosyl ganglioside (GM3) (d18:1/22:0), GM3 (d18:0/22:0), and phosphatidylserine (38:4) were combined. We found that a characteristic lipidome signature is associated with CAD in individuals with elevated HDL-C levels. Additionally, the disorders of sphingolipid as well as glycerophospholipid metabolism may underlie CAD.

A self-selected 16:8 time-restricted eating quasi-experimental intervention improves various markers of cardiovascular health in middle-age male cyclists

ObjectivesTime-restricted eating (TRE) is a dietary intervention that may offer some protection against cardiovascular disease (CVD), while also preserving performance in athletes. To date however, research on TRE in an active population has only been conducted in college-age cohorts and the effects of TRE in an older, trained population are less understood. Therefore, the aim of this study was to compare the effects of a 4-wk, 16:8 TRE intervention on markers of CVD risk in middle-age, male cyclists. MethodsParticipants (N = 12; age, 51.9 ± 8.6 y; training duration/wk, 375 ± 140 min; peak aerobic capacity, 41.8 ± 5.6 mL/kg/min) reported to the laboratory for two sessions (i.e., at baseline and post-TRE) where blood was drawn from an antecubital vein after an 8-h overnight fast. Dependent variables measured at baseline and post-TRE included insulin, cortisol, brain-derived neurotropic factor, free testosterone, thyroxine, triiodothyronine, C-reactive protein, advanced oxidative protein products, glutathione, tumor necrosis factor (TNF)-α, glucose, and a full lipid profile. ResultsCompared with baseline, TRE significantly lowered TNF-α (12.3 ± 3.4 versus 9.2 ± 2.4 pg/mL; P = 0.02) and glucose concentrations (93.4 ± 9.7 versus 87.5 ± 7.9 mg/dL; P = 0.01), as well as significantly elevated high-density lipoprotein cholesterol levels (45.7 ± 13.7 versus 49.2 ± 12.3 mg/dL; P = 0.04), respectively. No further significant changes were observed between the remaining variables (all P > 0.05). ConclusionOverall, these data suggest that incorporating a 4-wk TRE intervention with habitual endurance training can significantly improve some markers of CVD risk and may compliment the robust health benefits derived from a regular exercise regimen.

HDL - Quo vadis

Many epidemiological studies found low plasma levels of high-density lipoprotein (HDL) cholesterol (HDL-C) associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In cell culture and animal models, HDL particles show many anti-atherogenic actions. However, until now, clinical trials did not find any prevention of ASCVD events by drugs elevating HDL-C levels, at least not beyond statins. Also, genetic studies show no associations of HDL-C levels altering variants with cardiovascular risk. Therefore, the causal role and clinical benefit of HDL-C elevation in ASCVD are questioned. However, the interpretation of previous data has important limitations: First, the inverse relationship of HDL-C with the risk of ASCVD is limited to concentrations < 60 mg/dl (< 1.5 mmol/l). Higher concentrations do not reduce the risk of ASCVD events and are even associated with increased mortality. Therefore, neither the higher-the-better strategies of earlier drug developments nor the assumption of linear cause-and-effect relationships in Mendelian randomization trials are justified. Second, most of the drugs tested so far do not act specifically on HDL metabolism. Therefore, the futile endpoint studies question the clinical benefit of the investigated drugs, but not the importance of HDL in ASCVD. Third, the vascular functions of HDL are not exerted by its cholesterol content (i.e. HDL-C), but by a variety of other molecules. Comprehensive knowledge of the structure-function-disease relationships of HDL particles and their molecules is a prerequisite for testing their physiological and pathogenic relevance and possibly for optimizing the diagnosis and treatment of persons with HDL-associated risk of ASCVD, but also for other diseases, such as diabetes, chronic kidney disease, infections, autoimmune and neurodegenerative diseases.

Marein reduces lipid levels via modulating the PI3K/AKT/mTOR pathway to induce lipophagy

Ethnopharmacological relevanceThe capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. Aim of the studyThe study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. Materials and methodsBiochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. ResultsWe confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. ConclusionsOur study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.

San-wei-tan-xiang capsule attenuates atherosclerosis by increasing lysosomal activity in adipose tissue macrophages

Ethnopharmacological relevanceDyslipidemia is the leading risk factor of atherosclerosis (AS). Adipose tissue macrophages (ATMs) can regulate postprandial cholesterol levels via uptake and hydrolyzation of lipids and regulation of macrophage cholesterol efflux (MCE). San-wei-tan-xiang (SWTX) capsule, a Traditional Chinese medicine, exerts clinical benefits in patients with atherosclerotic cardiovascular diseases. Aim of the studyThis work is aimed to evaluate the chemical ingredients and mechanisms of SWTX in anti-AS. Materials and methodsThe chemical ingredients of SWTX identified by liquid chromatography coupled with tandem mass spectrometry were used for network pharmacological analysis. The atheroprotective function of SWTX was evaluated in ApoE−/− mice fed a cholesterol-enriched diet. ResultsThe chemical ingredients identified in SWTX were predicated to be important for lipid metabolism and AS. Animals studies suggested that SWTX effectively attenuated the atherosclerotic plaque growth, elevated postprandial HDL cholesterol levels, elevated the proportion of Tim4 and CD36-expressed ATMs, and upregulated the uptake of lipid and lysosomal activity in ATMs. SWTX-induced elevation of postprandial HDL cholesterol levels was dependent on increased lysosomal activity, since chloroquine, an inhibitor of lysosomal function, blocked the effect of SWTX. Lastly, some predicated bioactive compounds in SWTX can elevate lysosomal activity in vitro. ConclusionSWTX could attenuate atherosclerotic plaque formation by elevating lysosomal activity and enhancing MCE in ATMs.

U-shaped relationship between apolipoprotein A1 levels and mortality risk in men and women.

Apolipoprotein A1 (ApoA1) is the principal protein component of high-density lipoprotein (HDL). Although low HDL cholesterol (HDL-C) levels are known to be associated with greater cardiovascular risk, recent studies have also shown heightened mortality risk at very high HDL-C levels. To investigate the sex-specific association between elevated ApoA1 levels and adverse outcomes, and their genetic basis. A prospective cohort study of United Kingdom Biobank participants without coronary artery disease at enrollment was performed. The primary exposure was serum ApoA1 levels. The primary and secondary outcome measures were cardiovascular and all-cause death, respectively. In 402 783 participants followed for a median of 12.1 years, there was a U-shaped relationship between ApoA1 levels and both cardiovascular as well as all-cause mortality, after adjustment for traditional cardiovascular risk factors. Individuals in the highest decile of ApoA1 levels (1.91-2.50 g/L) demonstrated higher cardiovascular (HR 1.21, 95% CI 1.07-1.37, P < 0.0022) and all-cause mortality (HR 1.14, 95% CI 1.07-1.21, P < 0.0001) compared with those within the lowest risk eighth decile (1.67-1.75 g/L). The U-shaped relationship was present in both sexes, though more pronounced in men. Sensitivity analyses showed that cardiovascular mortality rates were higher in those with greater alcohol intake (P < 0.004). Adjustment for polygenic variation associated with higher ApoA1 levels did not attenuate the effect of very high ApoA1 levels on mortality. In the sub-group with very elevated HDL-C levels (> 80 mg/dL in men, > 100 mg/dL in women), there was no association between ApoA1 levels and mortality. Both very low and very elevated ApoA1 levels are associated with higher cardiovascular and all-cause mortality.