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  1. Article ; Online: Role of dietary interventions on microvascular health in South-Asian Surinamese people with type 2 diabetes in the Netherlands: A randomized controlled trial.

    van der Velden, Anouk I M / IJpelaar, Daphne H T / Chandie Shaw, Prataap K / Pijl, Hanno / Vink, Hans / van der Vlag, Johan / Rabelink, Ton J / van den Berg, Bernard M

    Nutrition & diabetes

    2024  Volume 14, Issue 1, Page(s) 17

    Abstract: Background/objectives: We investigated whether dietary interventions, i.e. a fasting mimicking diet (FMD, Prolon®) or glycocalyx mimetic supplementation (Endocalyx: Subjects/methods: A randomized, placebo controlled, 3-arm intervention study was ... ...

    Abstract Background/objectives: We investigated whether dietary interventions, i.e. a fasting mimicking diet (FMD, Prolon®) or glycocalyx mimetic supplementation (Endocalyx
    Subjects/methods: A randomized, placebo controlled, 3-arm intervention study was conducted in 56 SA-T2DM patients between 18 and 75 years old, for 3 consecutive months, with one additional follow up measurement 3 months after the last intervention. Sublingual microcirculation was assessed with SDF-imaging coupled to the GlycoCheck
    Results: Despite a temporal improvement in BMI and HbA1c after FMD the major treatment effect on microvascular health was worsening for RBC-velocity independent PBR
    Conclusions: We showed that despite temporal beneficial changes in BMI and HbA1c after FMD, this intervention is not able to preserve microvascular endothelial health in Dutch South-Asian patients with T2DM. In contrast, glycocalyx mimetics preserves the microvascular endothelial health and reduces the inflammatory cytokine MCP-1.
    Clinical study registration: NCT03889236.
    MeSH term(s) Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Diabetes Mellitus, Type 2 ; Glycated Hemoglobin ; Netherlands ; Diet ; Caribbean People ; South American People
    Chemical Substances Glycated Hemoglobin
    Language English
    Publishing date 2024-04-10
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2609314-5
    ISSN 2044-4052 ; 2044-4052
    ISSN (online) 2044-4052
    ISSN 2044-4052
    DOI 10.1038/s41387-024-00275-5
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  2. Article ; Online: Fasting mimicking diet in diabetic mice partially preserves glomerular endothelial glycocalyx coverage, without changing the diabetic metabolic environment.

    van der Velden, Anouk I M / Koudijs, Angela / Kooijman, Sander / Rietjens, Rosalie G J / Sol, Wendy M P J / Avramut, M Cristina / Wang, Gangqi / Rensen, Patrick C N / Rabelink, Ton J / van der Vlag, Johan / van den Berg, Bernard M

    American journal of physiology. Renal physiology

    2024  Volume 326, Issue 5, Page(s) F681–F693

    Abstract: Intermittent fasting has become of interest for its possible metabolic benefits and reduction of inflammation and oxidative damage, all of which play a role in the pathophysiology of diabetic nephropathy. We tested in a streptozotocin (60 mg/kg)-induced ... ...

    Abstract Intermittent fasting has become of interest for its possible metabolic benefits and reduction of inflammation and oxidative damage, all of which play a role in the pathophysiology of diabetic nephropathy. We tested in a streptozotocin (60 mg/kg)-induced diabetic apolipoprotein E knockout mouse model whether repeated fasting mimicking diet (FMD) prevents glomerular damage. Diabetic mice received 5 FMD cycles in 10 wk, and during cycles 1 and 5 caloric measurements were performed. After 10 wk, glomerular endothelial morphology was determined together with albuminuria, urinary heparanase-1 activity, and spatial mass spectrometry imaging to identify specific glomerular metabolic dysregulation. During FMD cycles, blood glucose levels dropped while a temporal metabolic switch was observed to increase fatty acid oxidation. Overall body weight at the end of the study was reduced together with albuminuria, although urine production was dramatically increased without affecting urinary heparanase-1 activity. Weight loss was found to be due to lean mass and water, not fat mass. Although capillary loop morphology and endothelial glycocalyx heparan sulfate contents were preserved, hyaluronan surface expression was reduced together with the presence of UDP-glucuronic acid. Mass spectrometry imaging further revealed reduced protein catabolic breakdown products and increased oxidative stress, not different from diabetic mice. In conclusion, although FMD preserves partially glomerular endothelial glycocalyx, loss of lean mass and increased glomerular oxidative stress argue whether such diet regimes are safe in patients with diabetes.
    MeSH term(s) Animals ; Glycocalyx/metabolism ; Glycocalyx/pathology ; Fasting ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/pathology ; Diabetic Nephropathies/physiopathology ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Oxidative Stress ; Male ; Blood Glucose/metabolism ; Albuminuria/metabolism ; Mice ; Glucuronidase/metabolism ; Mice, Knockout, ApoE ; Mice, Inbred C57BL ; Diet
    Chemical Substances Blood Glucose ; Glucuronidase (EC 3.2.1.31)
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00333.2023
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    Uc I Zs.89: Show issues Location:
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  3. Article ; Online: Sex-specific association between microvascular health and coagulation parameters: the Netherlands Epidemiology of Obesity study.

    Yuan, Lushun / Han, Jihee / van der Velden, Anouk I M / Vink, Hans / de Mutsert, Renée / Rosendaal, Frits R / van Hylckama Vlieg, Astrid / Li-Gao, Ruifang / Rabelink, Ton J / van den Berg, Bernard M

    Journal of thrombosis and haemostasis : JTH

    2023  Volume 21, Issue 9, Page(s) 2585–2595

    Abstract: Background: Microvascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. ... ...

    Abstract Background: Microvascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity.
    Objectives: We sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population.
    Methods: Using baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m
    Results: There was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBR
    Conclusion: We revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.
    MeSH term(s) Middle Aged ; Humans ; Male ; Female ; Netherlands/epidemiology ; Microcirculation/physiology ; Obesity/diagnosis ; Obesity/epidemiology ; Blood Coagulation ; Fibrinogen ; Coronary Disease
    Chemical Substances Fibrinogen (9001-32-5)
    Language English
    Publishing date 2023-06-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2023.06.001
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    Zs.MO 295: Show issues

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  4. Article ; Online: Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes.

    Rietjens, Rosalie G J / Wang, Gangqi / van der Velden, Anouk I M / Koudijs, Angela / Avramut, M Cristina / Kooijman, Sander / Rensen, Patrick C N / van der Vlag, Johan / Rabelink, Ton J / Heijs, Bram / van den Berg, Bernard M

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 6261

    Abstract: Diabetes is a main risk factor for kidney disease, causing diabetic nephropathy in close to half of all patients with diabetes. Metabolism has recently been identified to be decisive in cell fate decisions and repair. Here we used mass spectrometry ... ...

    Abstract Diabetes is a main risk factor for kidney disease, causing diabetic nephropathy in close to half of all patients with diabetes. Metabolism has recently been identified to be decisive in cell fate decisions and repair. Here we used mass spectrometry imaging (MSI) to identify tissue specific metabolic dysregulation, in order to better understand early diabetes-induced metabolic changes of renal cell types. In our experimental diabetes mouse model, early glomerular glycocalyx barrier loss and systemic metabolic changes were observed. In addition, MSI targeted at small molecule metabolites and glycero(phospho)lipids exposed distinct changes upon diabetes in downstream nephron segments. Interestingly, the outer stripe of the outer medullar proximal tubular segment (PT_S3) demonstrated the most distinct response compared to other segments. Furthermore, phosphatidylinositol lipid metabolism was altered specifically in PT_S3, with one of the phosphatidylinositol fatty acid tails being exchanged from longer unsaturated fatty acids to shorter, more saturated fatty acids. In acute kidney injury, the PT_S3 segment and its metabolism are already recognized as important factors in kidney repair processes. The current study exposes early diabetes-induced changes in membrane lipid composition in this PT_S3 segment as a hitherto unrecognized culprit in the early renal response to diabetes.
    MeSH term(s) Mice ; Animals ; Kidney/metabolism ; Kidney Tubules, Proximal/metabolism ; Kidney Tubules/metabolism ; Diabetic Nephropathies/metabolism ; Lipid Metabolism ; Diabetes Mellitus/metabolism
    Language English
    Publishing date 2023-04-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-33442-2
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  5. Article: Heparan sulfate mimetic fucoidan restores the endothelial glycocalyx and protects against dysfunction induced by serum of COVID-19 patients in the intensive care unit.

    Yuan, Lushun / Cheng, Shuzhen / Sol, Wendy M P J / van der Velden, Anouk I M / Vink, Hans / Rabelink, Ton J / van den Berg, Bernard M

    ERJ open research

    2022  Volume 8, Issue 2

    Abstract: Accumulating evidence proves that endothelial dysfunction is involved in coronavirus disease 2019 (COVID-19) progression. We previously demonstrated that the endothelial surface glycocalyx has a critical role in maintenance of vascular integrity. Here, ... ...

    Abstract Accumulating evidence proves that endothelial dysfunction is involved in coronavirus disease 2019 (COVID-19) progression. We previously demonstrated that the endothelial surface glycocalyx has a critical role in maintenance of vascular integrity. Here, we hypothesised that serum factors of severe COVID-19 patients affect the glycocalyx and result in endothelial dysfunction. We included blood samples of 32 COVID-19 hospitalised patients at the Leiden University Medical Center, of which 26 were hospitalised in an intensive care unit (ICU) and six on a non-ICU hospital floor; 18 of the samples were obtained from convalescent patients 6 weeks after hospital discharge, and 12 from age-matched healthy donors (control) during the first period of the outbreak. First, we determined endothelial (angiopoietin 2 (ANG2)) and glycocalyx degradation (soluble thrombomodulin (sTM) and syndecan-1 (sSDC1)) markers in plasma. In the plasma of COVID-19 patients, circulating ANG2 and sTM were elevated in patients in the ICU. Primary lung microvascular endothelial cell (HPMEC) and human glomerular microvascular endothelial cell (GEnC) cultured in the presence of these sera led to endothelial cell glycocalyx degradation, barrier disruption, inflammation and increased coagulation on the endothelial surface, significantly different compared to healthy control and non-ICU patient sera. These changes could all be restored in the presence of fucoidan. In conclusion, our data highlight the link between endothelial glycocalyx degradation, barrier failure and induction of a procoagulant surface in COVID-19 patients in ICU which could be targeted earlier in disease by the presence of heparan sulfate mimetics.
    Language English
    Publishing date 2022-05-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2827830-6
    ISSN 2312-0541
    ISSN 2312-0541
    DOI 10.1183/23120541.00652-2021
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  6. Article ; Online: Microvascular differences in individuals with obesity at risk of developing cardiovascular disease.

    van der Velden, Anouk I M / van den Berg, Bernard M / de Mutsert, Renée / van der Vlag, Johan / Jukema, J Wouter / Rosendaal, Frits R / Rabelink, Ton J / Vink, Hans

    Obesity (Silver Spring, Md.)

    2021  Volume 29, Issue 9, Page(s) 1439–1444

    Abstract: Objective: This study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease.: Methods: In this cross-sectional Netherlands Epidemiology of Obesity study, participant sublingual ... ...

    Abstract Objective: This study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease.
    Methods: In this cross-sectional Netherlands Epidemiology of Obesity study, participant sublingual microcirculation was assessed with a newly developed GlycoCheck software (Microvascular Health Solutions Inc., Salt Lake City, Utah), which integrates red blood cell velocity within the smallest capillaries (4-7 µm) and feed vessels (>10 µm). Framingham Risk Score was used to calculate 10-year cardiovascular risk, divided into low-, intermediate-, and high-risk groups. ANOVA was used to evaluate microvascular differences among the groups.
    Results: A total of 813 participants were included. The high-risk group (n = 168) was characterized by differences in the microvasculature compared with the low-risk group (n = 392): the high-risk group had a 49% reduction in the number of smallest capillaries and a 9.1-µm/s (95% CI: 5.2-12.9) higher red blood cell velocity in the feed vessels. No differences in velocity-corrected perfused boundary regions were found.
    Conclusions: It was observed that, with adding red blood cell velocity to the software, sidestream dark field imaging is able to detect microcirculatory differences in a cohort of individuals with obesity at risk for developing cardiovascular disease.
    MeSH term(s) Capillaries ; Cardiovascular Diseases/epidemiology ; Cross-Sectional Studies ; Humans ; Microcirculation ; Obesity/complications
    Language English
    Publishing date 2021-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2230457-5
    ISSN 1930-739X ; 1071-7323 ; 1930-7381
    ISSN (online) 1930-739X
    ISSN 1071-7323 ; 1930-7381
    DOI 10.1002/oby.23222
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    Zs.A 4061: Show issues Location:
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