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  1. Article ; Online: Dysfunctional HDL as a diagnostic and therapeutic target.

    Smith, Jonathan D

    Arteriosclerosis, thrombosis, and vascular biology

    2009  Volume 30, Issue 2, Page(s) 151–155

    Abstract: ... functionally similar. HDL and apolipoprotein A-I may become dysfunctional or even proinflammatory and ... for the development of an oxidant-resistant form of apoAI and clinical measures of HDL modification and dysfunction ... in reverse cholesterol transport and via its antiinflammatory properties. However, not all HDL is ...

    Abstract The atheroprotective effects of HDL are mediated by several mechanisms, including its role in reverse cholesterol transport and via its antiinflammatory properties. However, not all HDL is functionally similar. HDL and apolipoprotein A-I may become dysfunctional or even proinflammatory and thus promote atherosclerosis. ApoAI posttranslational modification can have a large impact on its function. Myeloperoxidase modification of apoAI impairs its function as a cholesterol acceptor, and the molecular changes induced by myeloperoxidase have been studied in detail. These studies provide the basis for the development of an oxidant-resistant form of apoAI and clinical measures of HDL modification and dysfunction, which may be useful as a treatment criterion.
    MeSH term(s) Animals ; Apolipoprotein A-I/metabolism ; Atherosclerosis/diagnosis ; Atherosclerosis/drug therapy ; Atherosclerosis/metabolism ; Biomarkers/metabolism ; Cholesterol/metabolism ; Humans ; Hypolipidemic Agents/therapeutic use ; Inflammation/diagnosis ; Inflammation/drug therapy ; Inflammation/metabolism ; Lipoproteins, HDL/metabolism ; Peroxidase/metabolism ; Predictive Value of Tests ; Protein Conformation ; Protein Processing, Post-Translational ; Structure-Activity Relationship
    Chemical Substances APOA1 protein, human ; Apolipoprotein A-I ; Biomarkers ; Hypolipidemic Agents ; Lipoproteins, HDL ; Cholesterol (97C5T2UQ7J) ; Peroxidase (EC 1.11.1.7)
    Language English
    Publishing date 2009-08-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.108.179226
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1705: Show issues Location:
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  2. Article ; Online: Dysfunctional HDL: a novel important diagnostic and therapeutic target in cardiovascular disease?

    Otocka-Kmiecik, Aneta / Mikhailidis, Dimitri P / Nicholls, Stephen J / Davidson, Michael / Rysz, Jacek / Banach, Maciej

    Progress in lipid research

    2012  Volume 51, Issue 4, Page(s) 314–324

    Abstract: ... and functional changes of HDL, which render the particles proinflammatory. Although therapeutic agents ... We review the current state of knowledge on the properties of HDL and factors/therapeutic agents ... which may restrain the transformation of normal HDL into dysfunctional HDL. ...

    Abstract High density lipoprotein (HDL) has many properties, which contribute to its atheroprotective role. However, some recent clinical trials have identified subjects with the progression of atherosclerosis despite normal levels of HDL cholesterol. This raises the question if all subfractions of HDL have the same properties. Moreover, recent investigations have shown that both acute and chronic inflammation may lead to structural and functional changes of HDL, which render the particles proinflammatory. Although therapeutic agents that increase HDL levels are now quite well established it is not clear whether they influence HDL quality. We review the current state of knowledge on the properties of HDL and factors/therapeutic agents which may restrain the transformation of normal HDL into dysfunctional HDL.
    MeSH term(s) Animals ; Apolipoproteins/antagonists & inhibitors ; Apolipoproteins/metabolism ; Azetidines/therapeutic use ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/metabolism ; Cholesterol Ester Transfer Proteins/antagonists & inhibitors ; Cholesterol Ester Transfer Proteins/metabolism ; Cholesterol, HDL/metabolism ; Ezetimibe ; Fibric Acids/therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Niacin/therapeutic use ; Peroxidase/antagonists & inhibitors ; Peroxidase/metabolism ; Thiazolidinediones/therapeutic use
    Chemical Substances Apolipoproteins ; Azetidines ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; Fibric Acids ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Thiazolidinediones ; Niacin (2679MF687A) ; Peroxidase (EC 1.11.1.7) ; Ezetimibe (EOR26LQQ24)
    Language English
    Publishing date 2012-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 282560-0
    ISSN 1873-2194 ; 0079-6832 ; 0163-7827
    ISSN (online) 1873-2194
    ISSN 0079-6832 ; 0163-7827
    DOI 10.1016/j.plipres.2012.03.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Dysfunctional HDL: A novel important diagnostic and therapeutic target in cardiovascular disease?

    Otocka-Kmiecik, Aneta / Mikhailidis, Dimitri P / Nicholls, Stephen J / Davidson, Michael / Rysz, Jacek / Banach, Maciej

    Progress in Lipid Research. 2012 Oct., v. 51, no. 4

    2012  

    Abstract: ... and functional changes of HDL, which render the particles proinflammatory. Although therapeutic agents ... We review the current state of knowledge on the properties of HDL and factors/therapeutic agents ... which may restrain the transformation of normal HDL into dysfunctional HDL. ...

    Abstract High density lipoprotein (HDL) has many properties, which contribute to its atheroprotective role. However, some recent clinical trials have identified subjects with the progression of atherosclerosis despite normal levels of HDL cholesterol. This raises the question if all subfractions of HDL have the same properties. Moreover, recent investigations have shown that both acute and chronic inflammation may lead to structural and functional changes of HDL, which render the particles proinflammatory. Although therapeutic agents that increase HDL levels are now quite well established it is not clear whether they influence HDL quality. We review the current state of knowledge on the properties of HDL and factors/therapeutic agents which may restrain the transformation of normal HDL into dysfunctional HDL.
    Keywords atherosclerosis ; clinical trials ; high density lipoprotein cholesterol ; inflammation
    Language English
    Dates of publication 2012-10
    Size p. 314-324.
    Publishing place Elsevier Ltd
    Document type Article
    ISSN 0163-7827
    DOI 10.1016/j.plipres.2012.03.003
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Modified and Dysfunctional Lipoproteins in Atherosclerosis: Effectors or Biomarkers?

    Orekhov, Alexander N / Sobenin, Igor A

    Current medicinal chemistry

    2018  Volume 26, Issue 9, Page(s) 1512–1524

    Abstract: ... for understanding whether lipoproteins are a therapeutic target or just diagnostic indicators. ... the mechanistic role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in atherogenesis ... discussed in this review is whether LDL and HDL are effectors or biomarkers, or both. This is important ...

    Abstract Atherosclerotic diseases are the leading cause of mortality in industrialized countries. Correspondingly, studying the pathogenesis of atherosclerosis and developing new methods for its diagnostic and treatment remain in the focus of current medicine and health care. This review aims to discuss the mechanistic role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in atherogenesis. In particular, the generally accepted hypothesis about the key role of oxidized LDL in atherogenesis is questioned, and an alternative concept of multiple modification of LDL is presented. The fundamental question discussed in this review is whether LDL and HDL are effectors or biomarkers, or both. This is important for understanding whether lipoproteins are a therapeutic target or just diagnostic indicators.
    MeSH term(s) Animals ; Atherosclerosis/metabolism ; Biomarkers/metabolism ; Humans ; Lipoproteins/metabolism
    Chemical Substances Biomarkers ; Lipoproteins
    Language English
    Publishing date 2018-03-20
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 1319315-6
    ISSN 1875-533X ; 0929-8673
    ISSN (online) 1875-533X
    ISSN 0929-8673
    DOI 10.2174/0929867325666180320121137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4432: Show issues Location:
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  5. Article: Sex-Specific Contribution of Cardiometabolic Index in Predicting Metabolic Dysfunction-Associated Fatty Liver Disease: Insights from a General Population.

    Gu, Dongxing / Lu, Yayun / Xu, Baiqing / Tang, Xuefeng

    Diabetes, metabolic syndrome and obesity : targets and therapy

    2023  Volume 16, Page(s) 3871–3883

    Abstract: ... HDL-C) by waist-to-height ratio (WHtR). Multivariable logistic regression analysis and restricted ... Background and objective: Evidence suggests that cardiometabolic index (CMI) has been identified ... as a novel obesity-related index associated with diabetes, hypertension, and cardiovascular disease. Current ...

    Abstract Background and objective: Evidence suggests that cardiometabolic index (CMI) has been identified as a novel obesity-related index associated with diabetes, hypertension, and cardiovascular disease. Current evidence suggests that the differences in sex hormones and regional fat distribution in both sexes are directly correlated with metabolic dysfunction-associated fatty liver disease (MAFLD) risk. This study aimed to investigate the diagnostic value of CMI in MAFLD in both sexes.
    Methods: This retrospective study included 6107 subjects who underwent annual health check-ups from March 2021 to January 2022. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariable logistic regression analysis and restricted cubic spline were used to investigate the association of CMI and MAFLD risk. Receiver operating characteristic curve analysis was conducted for the exploration of the diagnostic accuracies of obesity-related indicators. Areas under the curves (AUCs) with 95% CIs were calculated.
    Results: Prevalence of MAFLD increased with elevated quartiles of CMI in both sexes. The median (IQR) age was 46.00 (18.00) years. Multivariate logistic regression analyses showed that higher CMI was independently associated with MAFLD, in which every additional standard deviation (SD) of CMI increased the risk of MAFLD (OR=2.72, 95% CI:2.35-3.15 for males; OR=3.26, 95% CI:2.36-4.51 for females). Subjects in the fourth quartile of CMI had the highest odds of MAFLD for males (OR=15.82, 95% CI:11.84-21.14) and females (OR=22.60, 95% CI:9.52-53.65)(all P for trend<0.001). Besides, CMI had a non-linearity association with MAFLD (all P for non-linearity<0.001). Furthermore, CMI exhibited the largest AUC compared to other obesity-related indexes in terms of discriminating MAFLD in males (AUC=0.796, 95% CI:0.782-0.810) and females (AUC=0.853, 95% CI:0.834-0.872).
    Conclusion: CMI was a convenient indicator for the screening of MAFLD among Chinese adults. Females with high CMI had a better diagnostic value for MAFLD than males.
    Language English
    Publishing date 2023-11-30
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2494854-8
    ISSN 1178-7007
    ISSN 1178-7007
    DOI 10.2147/DMSO.S437413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells as Novel Diagnostic Tools for Non-Alcoholic Fatty Liver Disease: Visualizing Relationships with Known and Potential Disease Biomarkers.

    Garrafa, Emirena / Segala, Agnese / Vezzoli, Marika / Bottani, Emanuela / Zanini, Barbara / Vetturi, Alice / Bracale, Renata / Ricci, Chiara / Valerio, Alessandra

    Diagnostics (Basel, Switzerland)

    2023  Volume 13, Issue 14

    Abstract: ... respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response ... to current and novel therapies, including mitochondrial-targeted ones. ... prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently ...

    Abstract Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones.
    Language English
    Publishing date 2023-07-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics13142363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Endothelial dysfunction in hypopituitary adults with growth hormone deficiency.

    Evans, L M / Davies, J S / Goodfellow, J / Rees, J A / Scanlon, M F

    Clinical endocrinology

    1999  Volume 50, Issue 4, Page(s) 457–464

    Abstract: ... cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and ... inverse correlation between endothelial dysfunction and LDL-cholesterol suggests a possible aetiological ... replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range ...

    Abstract Objectives: Adult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age- and sex-matched controls.
    Patients: Seventeen hypopituitary adults with GHD (13 male, 4 female) aged 26-54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age- and sex-matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction.
    Measurements: Using an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium-dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium-independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF-1, and studied the relationship of these parameters to endothelial function.
    Results: Flow mediated endothelium-dependent dilatation (FMD), expressed as a percentage change from resting base-line diameter, was significantly impaired in the GHD group (3.70 +/- 2.36% vs. 7.30 +/- 2.42%, P < 0.001). In contrast, GTN-mediated dilatation was similar in both groups. There were no differences in total cholesterol, HDL cholesterol, LDL cholesterol or plasma triglyceride between the groups. Both fasting insulin (27.1 +/- 18.1 vs. 15.89 +/- 6.65 mU/l, P < 0.05) and glycated haemoglobin (HbA1c) levels (5.29 +/- 0.43 vs. 4.91 +/- 0.43%, P < 0.05) were significantly higher in the GHD group. FMD in both groups showed an inverse relationship with total cholesterol (r = -0.58, P < 0.05, GHD and r = -0.55, P < 0.05 controls). However, in the GHD subjects, there was a strong inverse relationship between FMD and LDL-cholesterol (r = -0.81, P < 0.0001). No other relationships were noted between FMD and any other metabolic parameters, or characteristics of GHD.
    Conclusions: Endothelial dysfunction is present in GH deficient adults prior to the onset of overt atherosclerotic disease. The similar glucose yet elevated fasting insulin levels imply a state of relative insulin insensitivity. The strong inverse correlation between endothelial dysfunction and LDL-cholesterol suggests a possible aetiological role for LDL-cholesterol in the pathogenesis of any excess cardiovascular risk associated with adult hypopituitarism.
    MeSH term(s) Adult ; Blood Glucose/analysis ; Brachial Artery/diagnostic imaging ; Cardiovascular Diseases/etiology ; Case-Control Studies ; Cholesterol, LDL/blood ; Endothelium, Vascular/physiopathology ; Female ; Growth Hormone/deficiency ; Humans ; Hypopituitarism/blood ; Hypopituitarism/physiopathology ; Insulin/blood ; Male ; Middle Aged ; Nitroglycerin ; Risk Factors ; Ultrasonography ; Vasodilation
    Chemical Substances Blood Glucose ; Cholesterol, LDL ; Insulin ; Growth Hormone (9002-72-6) ; Nitroglycerin (G59M7S0WS3)
    Language English
    Publishing date 1999-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 121745-8
    ISSN 1365-2265 ; 0300-0664
    ISSN (online) 1365-2265
    ISSN 0300-0664
    DOI 10.1046/j.1365-2265.1999.00671.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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