Leiden University Scholarly Publications

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Velden, A.I.M. van der (2024)

The glycocalyx: a diagnostic and therapeutic target in cardiometabolic diseases

Doctoral Thesis
Damage to the endothelial glycocalyx leads to endothelial dysfunction and microvascular changes, which can progress to the development cardiovascular complications. In type 2 diabetes, the pathogenic diabetic milieu induces structural changes in the endothelial glycocalyx. In this thesis, we investigate if microvascular changes can be detected and used as a diagnostic marker in individuals at risk of developing cardiovascular disease. Secondly, we show that urinary MCP-1 and HPSE-1 levels are correlated with the urinary albumin creatinine ratio in a multi-ethnic cohort of individuals with type 2 diabetes. Higher urinary MCP-1 levels can be found in individuals from Moroccan and South-Asian Surinamese descent. Lastly, we show a fasting mimicking diet is effective to reduce Hba1c end BMI in South-Asian Surinamese patients with diabetes, but did not improve the microvascular health. In the diabetic glomerulus, the loss of capillaries was prevented but increased oxidative stress was...Show moreDamage to the endothelial glycocalyx leads to endothelial dysfunction and microvascular changes, which can progress to the development cardiovascular complications. In type 2 diabetes, the pathogenic diabetic milieu induces structural changes in the endothelial glycocalyx. In this thesis, we investigate if microvascular changes can be detected and used as a diagnostic marker in individuals at risk of developing cardiovascular disease. Secondly, we show that urinary MCP-1 and HPSE-1 levels are correlated with the urinary albumin creatinine ratio in a multi-ethnic cohort of individuals with type 2 diabetes. Higher urinary MCP-1 levels can be found in individuals from Moroccan and South-Asian Surinamese descent. Lastly, we show a fasting mimicking diet is effective to reduce Hba1c end BMI in South-Asian Surinamese patients with diabetes, but did not improve the microvascular health. In the diabetic glomerulus, the loss of capillaries was prevented but increased oxidative stress was found. A supplement with glycocalyx mimetic did improve the microvascular health in South-Asian individuals and showed to preserve glomerular endothelial coverage in the experimental study.  In this thesis, we show that the endothelial glycocalyx can be used as a diagnostic marker for vascular health and can be used as a therapeutic target in type 2 diabetes.
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Endothelial glycocalyx
Cardiovascular diseases
Diabetes mellitus type 2
Diabetic nephropathy
Heparanase-1
South-Asian individuals
Fasting mimicking diet
Microvascular complications
Endothelial dysfunction
All authors
Velden, A.I.M. van der
Supervisor
Rabelink, A.J.
Co-supervisor
Berg, B.M. van den
Committee
Zonneveld, A.J. van; Pijl, H.; Bos, W.J.W.; Vlag, J. van der; IJpelaar, D.H.T.
Qualification
Doctor (dr.)
Awarding Institution
Leiden University Medical Center (LUMC), Leiden University
Date
2024-09-03
ISBN (print)
9789465100364