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1.
Ann Lab Med ; 43(1): 29-37, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36045054

RESUMO

Background: High LDL-cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is considered an important therapeutic target. It can be measured directly or calculated from the results of other lipid tests. The Friedewald formula is the most widely used formula for calculating LDL-C. We modified the Friedewald formula for a more accurate and practical estimation of LDL-C. Methods: Datasets, including measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-C concentrations were collected and assigned to derivation and validation sets. The datasets were further divided into five groups based on triglyceride concentrations. In the modified formula, LDL-C was defined as total cholesterol - HDL-cholesterol - (triglyceride/adjustment factor). For each group, the adjustment factor that minimized the difference between measured LDL-C and calculated LDL-C using modified formula was obtained. For validation, measured LDL-C and LDL-C calculated using the modified formula (LDL-CM), Friedewald formula (LDL-CF), Martin-Hopkins formula (LDL-CMa), and Sampson formula (LDL-CS) were compared. Results: In the derivation set, the adjustment factors were 4.7, 5.9, 6.3, and 6.4 for the groups with triglyceride concentrations <100, 101-200, 201-300, and >300 mg/dL, respectively. In the validation set, the coefficient of determination (R2) between measured and calculated LDL-C was higher for LDL-CM than for LDL-CF (R2=0.9330 vs. 0.9206). The agreement according to the National Cholesterol Education Program Adult Treatment Panel III classification of LDL-C was 86.36%, 86.08%, 86.82%, and 86.15% for LDL-CM, LDL-CF, LDL-CMa, and LDL-CS, respectively. Conclusions: We proposed a practical, improved LDL-C calculation formula by applying different factors depending on the triglyceride concentration.


Assuntos
Doenças Cardiovasculares , Hipercolesterolemia , Hiperlipidemias , Adulto , HDL-Colesterol , LDL-Colesterol , Humanos , Triglicerídeos
2.
Med Sci Monit ; 28: e937051, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36110037

RESUMO

Myocardial injury and necrosis caused by hyperlipidemia have been investigated by several researchers. Their pathogenesis and molecular basis are different from those of the more common clinical ischemic myocardial injury. Hyperlipidemia leads to peroxide accumulation in the cardiomyocytes, causes lipid overload, decreases the antioxidant capacity of the body, and promotes the inflammatory response. Furthermore, hyperlipidemia causes changes in the structure and function of mitochondria in the cardiomyocytes, which results in their injury and necrosis. Many previous studies have shown that metabolic diseases (eg, obesity and diabetes) and chemical poisoning can lead to hyperlipidemic myocardial injury and necrosis. Moreover, it has been observed that this pathological process can be inhibited by many small molecular substances. In the clinic, myocardial damage can be prevented or reduced by lowering the levels of triglyceride and cholesterol. Myocardial damage can also be regulated via the molecular pathway of myocardial injury caused by hyperlipidemia so that the disease can be treated. The present article reviewed the recent findings reported on the mechanisms of myocardial damage due to hyperlipidemia.


Assuntos
Hiperlipidemias , Antioxidantes/uso terapêutico , Humanos , Hiperlipidemias/tratamento farmacológico , Lipídeos , Necrose , Peróxidos/uso terapêutico , Triglicerídeos
3.
Nat Commun ; 13(1): 5461, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115863

RESUMO

Valvular inflammation triggered by hyperlipidemia has been considered as an important initial process of aortic valve disease; however, cellular and molecular evidence remains unclear. Here, we assess the relationship between plasma lipids and valvular inflammation, and identify association of low-density lipoprotein with increased valvular lipid and macrophage accumulation. Single-cell RNA sequencing analysis reveals the cellular heterogeneity of leukocytes, valvular interstitial cells, and valvular endothelial cells, and their phenotypic changes during hyperlipidemia leading to recruitment of monocyte-derived MHC-IIhi macrophages. Interestingly, we find activated PPARγ pathway in Cd36+ valvular endothelial cells increased in hyperlipidemic mice, and the conservation of PPARγ activation in non-calcified human aortic valves. While the PPARγ inhibition promotes inflammation, PPARγ activation using pioglitazone reduces valvular inflammation in hyperlipidemic mice. These results show that low-density lipoprotein is the main lipoprotein accumulated in the aortic valve during hyperlipidemia, leading to early-stage aortic valve disease, and PPARγ activation protects the aortic valve against inflammation.


Assuntos
Estenose da Valva Aórtica , Calcinose , Hiperlipidemias , Animais , Valva Aórtica/metabolismo , Calcinose/genética , Células Cultivadas , Células Endoteliais/metabolismo , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Imunomodulação , Inflamação/genética , Inflamação/metabolismo , Lipoproteínas LDL/metabolismo , Camundongos , PPAR gama/genética , PPAR gama/metabolismo , Pioglitazona/farmacologia , Transcriptoma
4.
J Investig Med High Impact Case Rep ; 10: 23247096221121393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36086824

RESUMO

Zieve syndrome presents with a triad of hemolytic anemia, unexplained jaundice, and hyperlipidemia secondary to alcohol use/alcohol-induced liver injury, highlighting hemolytic anemia as the hallmark feature. Zieve syndrome is more common than originally perceived as its incidence is estimated to be 1 in 1600 admissions, but its mechanism is still poorly understood. This is a case of a 29-year-old man who developed Zieve syndrome shortly after admission for pancreatitis secondary to alcohol use disorder. Early diagnosis is important to reduce unnecessary tests and interventions. Further studies should be considered to evaluate the association between Zieve syndrome and pancreatitis.


Assuntos
Alcoolismo , Anemia Hemolítica , Hiperlipidemias , Icterícia , Pancreatite , Adulto , Alcoolismo/complicações , Anemia Hemolítica/complicações , Humanos , Hiperlipidemias/complicações , Icterícia/complicações , Masculino , Pancreatite/complicações , Pancreatite/etiologia
6.
Biomed Pharmacother ; 154: 113640, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36081286

RESUMO

Atherosclerosis, the leading cause of cardiovascular disease responsible for the majority of deaths worldwide, cannot be sufficiently explained by established risk factors, including hypercholesterolemia. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. However, the role of homocysteine in atherosclerosis is still insufficiently understood. Previous research in this area has been also hampered by the lack of reproducible in vivo models of atherosclerosis that resemble the human situation. Here, we have developed and applied an automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development, even at low balloon pressure. Our automated system helped to glean vital details of cholesterol-independent changes in the aortic wall of balloon-injured rabbits. We show that deficiency of B vitamins, which are required for homocysteine degradation, leads to atherogenic transformation of the aorta resulting in accumulation of macrophages and lipids, impairment of its biomechanical properties and disorganization of aortic collagen/elastin in the absence of hypercholesterolemia. A combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity compared to any single condition. Our findings suggest that deficiency of B vitamins leads to atherogenic transformation of the aorta even in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.


Assuntos
Aterosclerose , Hipercolesterolemia , Hiperlipidemias , Complexo Vitamínico B , Animais , Aorta/metabolismo , Aterosclerose/metabolismo , Colesterol , Dieta Aterogênica , Homocisteína/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Hiperlipidemias/metabolismo , Coelhos
7.
Arthritis Res Ther ; 24(1): 211, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050780

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population. METHODS: All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations. RESULTS: We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85-1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58-0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13-1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96-1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11-2.87; and HR 3.19, 95% CI 2.31-4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12-1.54; and HR 2.06, 95% CI 1.38-3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81-1.69). CONCLUSIONS: The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.


Assuntos
Hiperlipidemias , Hipertensão , Lúpus Eritematoso Sistêmico , Osteoporose , Neoplasias do Colo do Útero , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Fatores de Risco , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem
8.
Cells ; 11(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36078077

RESUMO

Hyperlipidemia and type 2 diabetes (T2D) are major risk factors for atherosclerosis. Apoe-deficient (Apoe-/-) mice on certain genetic backgrounds develop hyperlipidemia, atherosclerosis, and T2D when fed a Western diet. Here, we sought to dissect phenotypic and genetic relationships of blood lipids and glucose with atherosclerotic plaque formation when the vasculature is exposed to high levels of cholesterol and glucose. Male F2 mice were generated from LP/J and BALB/cJ Apoe-/- mice and fed a Western diet for 12 weeks. Three significant QTL Ath51, Ath52 and Ath53 on chromosomes (Chr) 3 and 15 were mapped for atherosclerotic lesions. Ath52 on proximal Chr15 overlapped with QTL for plasma glucose, non-HDL cholesterol, and triglyceride. Atherosclerotic lesion sizes showed significant correlations with fasting, non-fasting glucose, non-fasting triglyceride, and body weight but no correlation with HDL, non-HDL cholesterol, and fasting triglyceride levels. Ath52 for atherosclerosis was down-graded from significant to suggestive level after adjustment for fasting, non-fasting glucose, and non-fasting triglyceride but minimally affected by HDL, non-HDL cholesterol, and fasting triglyceride. Adjustment for body weight suppressed Ath52 but elevated Ath53 on distal Chr15. These results demonstrate phenotypic and genetic connections of blood glucose and triglyceride with atherosclerosis, and suggest a more prominent role for blood glucose than cholesterol in atherosclerotic plaque formation of hyperlipidemic mice.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Hiperlipidemias , Placa Aterosclerótica , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/patologia , Glicemia , Peso Corporal/genética , Colesterol , Cruzamentos Genéticos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Hiperlipidemias/complicações , Hiperlipidemias/genética , Masculino , Camundongos , Camundongos Endogâmicos , Placa Aterosclerótica/genética , Locos de Características Quantitativas , Triglicerídeos
9.
J Am Heart Assoc ; 11(17): e027216, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36056728

RESUMO

Background The pathways of diastolic dysfunction and heart failure with preserved ejection fraction driven by lipotoxicity with metabolic syndrome are incompletely understood. Thus, there is an urgent need for animal models that accurately mimic the metabolic and cardiovascular phenotypes of this phenogroup for mechanistic studies. Methods and Results Hyperlipidemia was induced in WT-129 mice by 4 weeks of biweekly poloxamer-407 intraperitoneal injections with or without a single intravenous injection of adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor (n=31), or single intravenous injection with adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor alone (n=10). Treatment groups were compared with untreated or placebo controls (n=37). Echocardiography, blood pressure, whole-body plethysmography, ECG telemetry, activity wheel monitoring, and biochemical and histological changes were assessed at 4 to 8 weeks. At 4 weeks, double treatment conferred diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Blood pressure and whole-body plethysmography results were normal, but respiration decreased at 8 weeks (P<0.01). ECG and activity wheel monitoring, respectively, indicated heart block and decreased exercise activity (P<0.001). Double treatment promoted elevated myocardial lipids including total cholesterol, fibrosis, increased wet/dry lung (P<0.001) and heart weight/body weight (P<0.05). Xanthelasma, ascites, and cardiac ischemia were evident in double and single (p407) groups. Sudden death occurred between 6 and 12 weeks in double and single (p407) treatment groups. Conclusions We present a novel model of heart failure with preserved ejection fraction driven by dyslipidemia where mice acquire diastolic dysfunction, arrhythmia, cardiac hypertrophy, fibrosis, pulmonary congestion, exercise intolerance, and preserved ejection fraction in the absence of obesity, hypertension, kidney disease, or diabetes. The model can be applied to dissect pathways of metabolic syndrome that drive diastolic dysfunction in this lipotoxicity-mediated heart failure with preserved ejection fraction phenogroup mimic.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Hiperlipidemias , Síndrome Metabólica , Animais , Modelos Animais de Doenças , Hiperlipidemias/complicações , Lipoproteínas LDL , Camundongos , Volume Sistólico/fisiologia , Troponina T , Função Ventricular Esquerda/fisiologia
10.
Metabolomics ; 18(10): 75, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36125563

RESUMO

INTRODUCTION: The effects of lipopolysaccharides (i.e., endotoxin; LPS) on metabolism are poorly defined in lactating dairy cattle experiencing hyperlipidemia. OBJECTIVES: Our objective was to explore the effects of acute intravenous LPS administration on metabolism in late-lactation Holstein cows experiencing hyperlipidemia induced by intravenous triglyceride infusion and feed restriction. METHODS: Ten non-pregnant lactating Holstein cows (273 ± 35 d in milk) were administered a single bolus of saline (3 mL of saline; n [Formula: see text] 5) or LPS (0.375 [Formula: see text]g of LPS/kg of body weight; n [Formula: see text] 5). Simultaneously, cows were intravenously infused a triglyceride emulsion and feed restricted for 16 h to induce hyperlipidemia in an attempt to model the periparturient period. Blood was sampled at routine intervals. Changes in circulating total fatty acid concentrations and inflammatory parameters were measured. Plasma samples were analyzed using untargeted lipidomics and metabolomics. RESULTS: Endotoxin increased circulating serum amyloid A, LPS-binding protein, and cortisol concentrations. Endotoxin administration decreased plasma lysophosphatidylcholine (LPC) concentrations and increased select plasma ceramide concentrations. These outcomes suggest modulation of the immune response and insulin action. Lipopolysaccharide decreased the ratio of phosphatidylcholine to phosphatidylethanomanine, which potentially indicate a decrease in the hepatic activation of phosphatidylethanolamine N-methyltransferase and triglyceride export. Endotoxin administration also increased plasma concentrations of pyruvic and lactic acids, and decreased plasma citric acid concentrations, which implicate the upregulation of glycolysis and downregulation of the citric acid cycle (i.e., the Warburg effect), potentially in leukocytes. CONCLUSION: Acute intravenous LPS administration decreased circulating LPC concentrations, modified ceramide and glycerophospholipid concentrations, and influenced intermediary metabolism in dairy cows experiencing hyperlipidemia.


Assuntos
Hiperlipidemias , Insulinas , Animais , Bovinos , Ceramidas , Ácido Cítrico , Emulsões/farmacologia , Endotoxinas/farmacologia , Ácidos Graxos , Feminino , Glicerofosfolipídeos , Hidrocortisona/farmacologia , Hiperlipidemias/induzido quimicamente , Insulinas/farmacologia , Lactação , Lipidômica , Lipopolissacarídeos/farmacologia , Lisofosfatidilcolinas/farmacologia , Metaboloma , Metabolômica , Fosfatidilcolinas , Fosfatidiletanolamina N-Metiltransferase/farmacologia , Proteína Amiloide A Sérica , Triglicerídeos
11.
Dtsch Med Wochenschr ; 147(19): 1286-1295, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-36126928

RESUMO

Elevated triglycerides and their lipidological consequences (small, dense LDL, residual particles (remnants), reduced HDL cholesterol) are an important and independent cardiovascular risk factor. Particularly in diabetes mellitus, hypertriglyceridemia is regarded as the main cause of high cardiovascular morbidity and mortality; very high triglyceride levels can cause acute pancreatitis. This article provides an overview of the current scientific status of the pathogenesis and clinical significance of hypertriglyceridemia.


Assuntos
Doenças Cardiovasculares , Hiperlipidemias , Hipertrigliceridemia , Pancreatite , Doença Aguda , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol , Objetivos , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/terapia , Fatores de Risco , Triglicerídeos
12.
PLoS One ; 17(9): e0274066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36083972

RESUMO

BACKGROUND: Retinitis pigmentosa (RP) is the most frequent retinal hereditary dystrophy and result in blindness if progresses. Several case reports have revealed the possible association between RP and primary angle-closure glaucoma (PACG). We conducted a population-based study to explore whether RP significantly increased the risk of PACG development. METHODS: Using the Taiwan National Health Insurance Research Database, we enrolled patients with RP into the RP group from 2001 to 2013 and included a comparison group of 1:4 age- and sex-matched individuals without RP. We performed a Cox regression analysis to estimate the crude and adjusted hazard ratios (HRs) of RP for PACG after adjustment for hypertension, diabetes, hyperlipidaemia, chronic kidney disease, and lens subluxation. RESULTS: We enrolled 6223 subjects with RP and 24892 subjects for comparison. The mean age of the cohort was 49.0 ± 18.1 years. The RP group had significantly higher percentages of diabetes mellitus, hypertension, and hyperlipidaemia. The cumulative incidence of PACG in patients with RP was 1.61%, which was significantly higher than that in the comparison group (0.81%, p < 0.0001). According to the univariate Cox regression analysis, the hazard of PACG development was significantly greater in the RP group, with an unadjusted HR of 2.09 (95% confidence interval [CI], 1.64-2.65). The increased risk persisted after adjusting for confounders (adjusted HR = 2.18; 95% CI, 1.76-2.72). CONCLUSION: This nationwide population-based cohort study showed that people with RP are at a significantly greater risk of developing PACG than individuals without RP.


Assuntos
Diabetes Mellitus , Glaucoma de Ângulo Fechado , Hiperlipidemias , Hipertensão , Retinite Pigmentosa , Adulto , Idoso , Estudos de Coortes , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/epidemiologia , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Retinite Pigmentosa/complicações , Retinite Pigmentosa/epidemiologia
13.
Nutrients ; 14(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36079733

RESUMO

Obesity is frequently associated with dysregulated lipid metabolism and lipotoxicity. Inonotus hispidus (Bull.: Fr.) P. Karst (IH) is an edible and medicinal parasitic mushroom. In this study, after a systematic analysis of its nutritional ingredients, the regulatory effects of IH on lipid metabolism were investigated in mice fed a high-fat diet (HFD). In HFD-fed mice, IH reversed the pathological state of the liver and the three types of fat and significantly decreased the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and leptin (LEP) and increased the level of high-density liptein cholesterol (HDL-C) in serum. Meanwhile, IH ameliorated liver damage by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) levels in the liver and serum. Compared with HFD-fed mice, IH significantly modulated the gut microbiota, changed the relative abundances of microflora at different taxonomic levels, and regulated lipid levels. The results showed that 30 differential lipids were found. Results from Western blotting confirmed that IH regulated the nuclear factor erythroid-2 related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling pathway and oxidative stress. This study aimed to provide experimental evidence for the applicability of IH in obesity treatment.


Assuntos
Dieta Hiperlipídica , Hiperlipidemias , Animais , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/metabolismo , Inflamação/metabolismo , Inonotus , Fígado/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Obesidade/metabolismo , Estresse Oxidativo , Transdução de Sinais
14.
J Transl Med ; 20(1): 412, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076294

RESUMO

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology. METHODS: HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology. RESULTS: The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP. CONCLUSIONS: In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.


Assuntos
Berberina , Hiperlipidemias , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Cricetinae , Humanos , Hiperlipidemias/tratamento farmacológico , Lipidômica , Lipídeos , Farmacologia em Rede
15.
Lipids Health Dis ; 21(1): 90, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123608

RESUMO

OBJECTIVE: We wanted to explore how angiopoietin-like 3 (ANGPTL3) impact hyperlipidemia-induced renal injury. METHODS: ANGPTL3 knockout mice and wild-type C57 mice were set up in four groups (N = 5) depending on a normal or 60% high-fat diet: wild-type with normal diet (WT), angptl3-/- with normal diet (KO), wild-type + high-fat diet (WT + HF) and angptl3-/- + high-fat diet (KO + HF). The detection time points were the 9th, 13th, 17th and 21st weeks after modeling. Serum lipid and urinary protein levels of mice in each group were detected, and pathological changes in the kidney were analyzed. Moreover, the expression of ANGPTL3, α-actinin-4 (ACTN4), CD2-associated protein (CD2AP) and podocin was tested in the glomerulus by immunohistochemistry (IHC). RESULTS: In the WT + HF group, hyperlipidemia and proteinuria could be observed at the 9th week and were gradually aggravated with time. Compared with WT + HF mice, the levels of serum lipids and proteinuria in KO + HF mice were significantly reduced, and the width of podocyte foot processes (FPs) fusion was also markedly improved. The IHC results suggested that in WT + HF mice, the expression of ANGPTL3 was significantly enhanced. After modeling, ACTN4 expression was markedly weakened in the glomeruli of WT + HF mice. Different to WT mice, ACTN4 expression was not observed obviously change in KO + HF mice. Compared with the normal diet group, the expression of podocin showed a decline in WT mice treated with high-fat diet and showed a significant difference from the 17th week. In addition, podocin expression in KO + HF glomeruli was also found to be weak but not significantly different from that in WT + HF glomeruli at the four time points. The expression of CD2AP showed similar results among the four groups. CONCLUSION: ANGPTL3 could play a role in the mechanism of hyperlipidemia-associated podocyte injury via ACTN4.


Assuntos
Dieta Hiperlipídica , Hiperlipidemias , Actinina/genética , Proteína 3 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/genética , Proteínas Semelhantes a Angiopoietina/metabolismo , Angiopoietinas , Animais , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Rim/metabolismo , Lipídeos , Camundongos , Camundongos Knockout , Proteinúria
16.
Lipids Health Dis ; 21(1): 88, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123675

RESUMO

BACKGROUND: Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth. METHODS: One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve. RESULTS: Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P < 0.05). The ideal values of FMR in diagnosing dyslipidaemia were 0.2224 for males and 0.4809 for females, while males had a higher AUC than females (0.7118 vs. 0.6656). Meanwhile, high FMR values were significantly associated with adverse outcomes of dyslipidaemia, hypercholesterolemia and hypertriglyceridaemia (P < 0.05). CONCLUSIONS: The FMR was positively correlated with the prevalence of dyslipidaemia. The FMR can be used as an effective body composition index for diagnosing dyslipidaemia, especially in males, and preventive strategies should be initiated in transitional-age youth to decrease obesity-related dyslipidaemia.


Assuntos
Dislipidemias , Hiperlipidemias , Adolescente , Adulto , Antropometria , Índice de Massa Corporal , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Masculino , Músculos , Obesidade
17.
Curr Opin Lipidol ; 33(4): 227-230, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35942808

RESUMO

PURPOSE OF REVIEW: In recent years, there has been interest for the development of simplified diagnosis algorithms of dysbetalipoproteinemia (DBL) in order to avoid the complex testing associated with the Fredrickson criteria (reference method). The purpose of this review is to present recent advances in the field of DBL with a focus on screening and diagnosis. RECENT FINDINGS: Recently, two different multi-step algorithms for the diagnosis of DBL have been published and their performance has been compared to the Fredrickson criteria. Furthermore, a recent large study demonstrated that only a minority (38%) of DBL patients are carriers of the E2/E2 genotype and that these individuals presented a more severe phenotype. SUMMARY: The current literature supports the fact that the DBL phenotype is more heterogeneous and complex than previously thought. Indeed, DBL patients can present with either mild or more severe phenotypes that can be distinguished as multifactorial remnant cholesterol disease and genetic apolipoprotein B deficiency. Measurement of apolipoprotein B as well as APOE gene testing are both essential elements in the diagnosis of DBL.


Assuntos
Hiperlipidemias , Hiperlipoproteinemia Tipo III , Apolipoproteína B-100 , Apolipoproteínas B/genética , Apolipoproteínas E/genética , Colesterol , Genótipo , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/genética , Hiperlipoproteinemia Tipo III/diagnóstico , Hiperlipoproteinemia Tipo III/genética
18.
Curr Opin Endocrinol Diabetes Obes ; 29(5): 420-426, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35943187

RESUMO

PURPOSE OF REVIEW: Cardiovascular disease remains one of the leading causes of morbidity and mortality today. The major risk factors for cardiovascular disease include type 2 diabetes mellitus, hypertension, tobacco smoking, elevated body mass index, and hyperlipidemia. The decision to use medication treatment for hyperlipidemia can be assisted using computerized decision tools. RECENT FINDINGS: The treatment of hyperlipidemia with 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has become widely recommended even though most people treated with them do not get clinical benefit, and the magnitude of their effect is dependent upon prior clinical risk. This article reviews recent research about the effectiveness of HMG-CoA reductase inhibitors, and the use of decision-making tools to assist the clinician in advising patients about the use of these medications. SUMMARY: On-line decision tools are available to estimate cardiovascular risk and to assist clinicians in helping their patients make their own decision about whether to take HMG-CoA reductase inhibitor medication to reduce cardiovascular risk.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Técnicas de Apoio para a Decisão , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores de Risco
19.
Curr Opin Endocrinol Diabetes Obes ; 29(5): 497-511, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35938780

RESUMO

PURPOSE OF REVIEW: Although there is an extensive literature on the efficacy of the low carbohydrate diet (LCD) for weight loss and in the management of type 2 diabetes, concerns have been raised that the LCD may increase cardiovascular disease (CVD) risk by increasing the level of low-density lipoprotein cholesterol (LDL-C). We have assessed the value of LDL-C as a CVD risk factor, as well as effects of the LCD on other CVD risk factors. We have also reviewed findings that provide guidance as to whether statin therapy would be beneficial for individuals with high LDL-C on an LCD. RECENT FINDINGS: Multiple longitudinal trials have demonstrated the safety and effectiveness of the LCD, while also providing evidence of improvements in the most reliable CVD risk factors. Recent findings have also confirmed how ineffective LDL-C is in predicting CVD risk. SUMMARY: Extensive research has demonstrated the efficacy of the LCD to improve the most robust CVD risk factors, such as hyperglycemia, hypertension, and atherogenic dyslipidemia. Our review of the literature indicates that statin therapy for both primary and secondary prevention of CVD is not warranted for individuals on an LCD with elevated LDL-C who have achieved a low triglyceride/HDL ratio.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol , LDL-Colesterol , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta com Restrição de Carboidratos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Fatores de Risco
20.
BMJ Case Rep ; 15(8)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038155

RESUMO

A woman in her 30s with gestational diabetes presented at 36 weeks' gestation with reduced fetal movements and diminishing insulin requirements. In view of her gestation, she was induced and incidentally found to have profound hyponatraemia. Further biochemical investigations confirmed severe hypertriglyceridaemia and hypercholesterolaemia. This raises the possibility of secondary causes such as familial dysbetalipoproteinemia and polygenetic hypertriglyceridaemia. She was successfully managed by aggressive dietary modification. This involved a supervised fast followed by a fat-free diet. A fenofibrate was proposed but declined due to our patient's wish to breastfeed. Management required considerable input from the multidisciplinary team. Treatment options to consider are aggressive dietary restriction of fat or the addition of a cholesterol-lowering medication, such as a fibrate. In refractory cases, a supervised fast may be required or, in cases where complications have arisen, apheresis. The patient and her baby made a good recovery with no long-lasting health implications.


Assuntos
Fenofibrato , Hiperlipidemias , Hipertrigliceridemia , Dieta com Restrição de Gorduras , Feminino , Fenofibrato/uso terapêutico , Humanos , Hiperlipidemias/complicações , Hipertrigliceridemia/complicações , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/terapia , Gravidez
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