Cees Vermeer

Cees Vermeer
Maastricht University | UM

PhD

About

454
Publications
116,569
Reads
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20,819
Citations
Introduction
Cees Vermeer has worked for over 40 years as a research leader and principal investigator at Maastricht University. Although presently retired, he is still active: 1) in publishing his latest results and 2) as a discussion partner for colleagues in Maastricht and elsewhere. During his active career he has investigated the importance of vitamin K for a wide range of physiological processes, and the function of vitamin K-dependent proteins, notably those not involved in blood coagulation. Presently, he is regarded as one of the global key opinion leaders in the vitamin K area.
Additional affiliations
March 2001 - present
Iuliu Hațieganu University of Medicine and Pharmacy
Position
  • Doctor Honoris causa
January 2001 - October 2017
Maastricht University
Position
  • Principal Investigator
January 1994 - December 1994
World Health Organization WHO
Position
  • Temporary Advisor

Publications

Publications (454)
Article
Full-text available
Calciphylaxis is a rare, yet underdiagnosed condition causing high mortality in patients with severe renal and cardiovascular disease. Since knowledge of the pathophysiology of calciphylaxis is limited, a differential analysis of histological alterations in patient subgroups with various comorbidities might expose different disease phenotypes and a...
Article
Full-text available
Objectives: Vitamin K deficiency consistently associates with worse clinical outcome in COVID-19 patients. However, whether this is due to increased expenditure during inflammation or poor vitamin K status prior to infection remained unknown. Methods: Dp-ucMGP levels of 128 individuals were measured for the post-MONICA study and were compared to...
Article
Full-text available
We conclude that the correlation between dp-ucMGP and creatinine is far more likely the result of vitamin K deficiency than a function of a decreased glomerular filtration rate. Regardless of any renal influence on dp-ucMGP levels, elevated dp-ucMGP levels should, in our opinion, be normalized by vitamin K administration and not through adjusting f...
Article
Background and aims: Matrix Gla protein (MGP), a vitamin K-dependent protein, is a potent inhibitor of vascular calcification. Desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K insufficiency, has been shown to predict cardiovascular disease (CVD) and all-cause mortality in high-risk populations. Whether the increased risk associated...
Article
Full-text available
Chronic inflammation is a major driver of chronic inflammatory diseases (CIDs), with a tremendous impact worldwide. Besides its function as a pathological calcification inhibitor, vitamin K-dependent protein Gla-rich protein (GRP) was shown to act as an anti-inflammatory agent independently of its gamma-carboxylation status. Although GRP’s therapeu...
Article
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Sobczyk and Gaunt genetically predicted circulating zinc, selenium, copper, and vitamin K1 levels—instead of directly measuring nutrients in blood—and hypothesized that these levels would associate with SARS-CoV-2 infection and COVID-19 severity [...]
Article
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Bovine meat provides healthy nutrients but has also been negatively linked to greenhouse gases and non-communicable diseases. A double-blind intervention study was carried out to compare beef meat from bulls fed with feed supplemented with selenium, vitamin D, E, K (SeDEK-feed), and n-3, or REGULAR feed. Thirty-four young healthy women (19–29 years...
Article
Full-text available
Matrix Gla protein (MGP), a local inhibitor of tissue mineralization, is associated with vascular calcification. Depending on the carboxylation and phosphorylation status, MGP has active conformations, e.g., carboxylated MGP (cMGP) and phosphorylated MGP (pMGP), but also inactive conformations, e.g., uncarboxylated MGP (ucMGP) and dephosphorylated...
Article
Aim: We explored whether matrix Gla protein (MGP, natural calcification inhibitor) and sclerostin (glycoprotein responsible for osteoblast differentiation) interact in terms of mortality risk in coronary patients. Methods: 945 patients after myocardial infarction and/or coronary revascularization were followed in a prospective study. All-cause deat...
Article
Full-text available
Meningiomas are classified by the World Health Organization (WHO) in three grades, based on morphological features. Independent of this grading, the presence of calcification in meningiomas influences their growth rate. The messenger RNA of matrix Gla protein (MGP), an extra-hepatic protein with different conformations involved in the homeostasis o...
Article
Full-text available
Introduction Gla rich protein (GRP) is a vitamin K dependent protein, shown to function as an inhibitor of pathological calcification and as an anti-inflammatory agent, with potential therapeutic use for age-related diseases such as osteoarthritis (OA) [1,2]. OA is a leading cause of disability and morbidity in the older population and constitutes...
Article
Full-text available
Osteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline design...
Article
Full-text available
Coronavirus disease 2019 (Covid-19), caused by SARS-CoV-2, exerts far-reaching effects on public health and socioeconomic welfare. The majority of infected individuals have mild to moderate symptoms but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes t...
Article
Full-text available
Background: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods: Lower limb arterial calcification scores wer...
Article
Background and Aims Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification critically dependent on circulating vitamin K status. Growth differentiation factor 15 (GDF-15) is a regulatory cytokine mainly of the inflammatory and angiogenesis pathways, but potentially also involved in bone mineralization. We sought to determine whet...
Article
Full-text available
Background: Matrix Gla-Protein (MGP) is involved in the prevention of arterial calcification. During vitamin K-insufficiency, MGP is produced in its inactive form: dp-ucMGP. Two 3-year intervention studies in the general population have shown that increased vitamin K intake may decrease arterial stiffening, but the difference with placebo became on...
Conference Paper
Full-text available
The rupture of atherosclerotic plaques is the prerequisite for adverse cardiovascular events. Calcification morphology plays a critical role in plaque stability, therefore accurate calcification classification is essential for favourable patient management. Blood biomarkers may be a worthwhile approach to stratify patients based on calcification ph...
Article
Purpose Schnyder corneal dystrophy (SCD) is a rare autosomal dominant disorder characterized by corneal lipid accumulation and caused by UBIAD1 pathogenic variants. UBIAD1 encodes a vitamin K (VK) biosynthetic enzyme. To assess the corneal and vascular VK status in SCD patients, we focused on matrix Gla protein (MGP), a VK‐dependent protein. Metho...
Preprint
Full-text available
Background: Lower limb arterial calcification is a frequent, underestimated but serious diabetic complication. The DIACART study is a prospective cohort study designed to evaluate the determinants of lower limb arterial calcification progression in 198 patients with Type 2 Diabetes. Methods: Lower limb arterial calcification score was determined by...
Preprint
Full-text available
Background: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods: Lower limb arterial calcification scores were d...
Article
Full-text available
Calcified meningiomas have a slower growth rate and a better outcome than non-calcified meningiomas. Matrix Gla Protein (MGP) acts as an inhibitor of soft tissue calcification. Depending on its carboxylation status MGP may occur in two conformations: uncarboxylated (ucMGP) or carboxylated (cMGP). Low levels of serum ucMGP have been described to be...
Article
Full-text available
Aims/Hypothesis Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated...
Article
Vitamin K is present in the testes though its actual function in male reproduction is poorly understood. This study investigated the harmful effect of extrahepatic vitamin K insufficiency on the testicular structure. Sprague‐Dawley rats were fed with a diet containing warfarin for 2, 4 and 8 weeks; control animals received a standard diet without w...
Article
Full-text available
Background Increased renal resistive index ( RRI ) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (γ‐carboxyglutamate) protein ( MGP ) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho‐uncarboxylated MGP [dp‐uc MGP ]) has been associated with vascular stiffness, c...
Article
Full-text available
Elastin degradation is accelerated in chronic obstructive pulmonary disease (COPD) and is partially regulated by Matrix Gla Protein (MGP), via a vitamin K-dependent pathway. The aim was to assess vitamin K status in COPD as well as associations between vitamin K status, elastin degradation, lung function parameters and mortality. A total of 192 COP...
Article
Full-text available
Background Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K–dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that the central hemodynamic properties might be associated with inactive desphospho‐u...
Article
Introduction: Osteoarthritis (OA) is a whole-joint disease where inflammation interplays with extracellular matrix mineralization in a cycle that leads to its degradation. The lack of effective preventing treatments and disease modifying agents, demands new therapeutic targets and development of effective drugs. Amentadione (YP), a meroditerpenoid...
Data
Table S1. Central Hemodynamic Characteristics by Tertiles of the dp‐ucMGP Distribution Table S2. Hemodynamic Traits in the Top Quintile versus the Other Quintiles of the dp‐ucMGP Distribution Table S3. Correlates of Central Blood Pressure and the Augmentation Ratio and Augmentation Index Table S4. Correlates of Pulse Wave Velocity, the Forward a...
Article
Rapid progression of vascular calcification (VC) in hemodialysis (HD) patients is caused by several factors including inflammation and an imbalance between active inducers and inhibitors of VC. Growing evidence shows that online hemodiafiltration (ol-HDF), a combination of diffusive and convective solute transport, has positive effects on the uremi...
Article
Full-text available
Objective: This study aims to investigate whether plasma matrix Gla protein (MGP) species, desphospho-uncarboxylated (dp-uc) MGP, and total uncarboxylated (t-uc) MGP are associated with plaque levels of uncarboxylated (uc) MGP, markers of plaque stability, and cardiovascular disease (CVD) risk. Methods: From the Athero-Express biobank, we select...
Article
Full-text available
Abstract Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly...
Article
Vascular calcification leads to increased large artery stiffness. Matrix gla-protein (MGP) is a vitamin K-dependent protein that inhibits arterial calcification. Aldosterone promotes vascular calcification and stiffness, but the relationships between aldosterone, MGP, and arterial stiffness are unknown. We studied 199 adults (predominantly older me...
Article
Full-text available
Background: Matrix Gla protein (MGP) is a vascular calcification inhibitor dependent upon vitamin K for activation. Evidence suggests that elevated plasma inactive MGP levels (desphospho-uncarboxylated MGP, dp-ucMGP; indicating poorer vascular vitamin K status) are associated with greater cardiovascular disease (CVD) risk. Despite African American...
Article
Full-text available
Vitamin K₂ (menaquinone) concentrations were measured in a wide range of cheeses and the effects of fat content, ripening and origin of the cheeses were investigated. Moreover, the menaquinone content of cheese was compared with that of other foods known to contain vitamin K₂. It was found that cheese and curd are the most important sources of long...
Article
Full-text available
Recent studies showing an inverse association between estimated glomerular filtration rate (eGFR), a microvas-cular trait, and inactive desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) support the hypothesis that after vitamin K-dependent activation, matrix Gla protein (MGP) is renopro-tective, but these were limited by their cross-sectional...
Article
Full-text available
Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not f...
Article
Full-text available
Objectives A novel paradigm of diastolic left ventricular (LV) dysfunction proposes involvement of the cardiac microvasculature. Vitamin K dependent matrix Gla protein (MGP) plays a role in preserving microcirculatory integrity. We hypothesized that LV filling pressure–a measure of diastolic LV dysfunction–increases with higher plasma level of inac...
Article
Micronutrients are essential to health at every life stage and their deficiencies are associated with increased incidence of various pathophysiological states and poor quality of life. Efficient methods are therefore needed to monitor micronutrient status of individuals and to improve evidenced-based recommendations for populations. This review (i)...
Article
Full-text available
Background: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation o...
Article
Objective: Inhibition of mineral crystal formation is a crucial step in ectopic calcification. Serum calciprotein particles (CPPs) have been linked to chronic kidney disease (CKD) calcification propensity, but additional knowledge is required to understand their function, assemblage, and composition. The role of other circulating nanostructures, s...
Article
Full-text available
Background/objectives: Vitamin K status has been linked to fat and glucose metabolism by several authors, but whether high vitamin K intake influences body weight or composition has remained unclear. Here we tested the hypothesis that increased vitamin K intake decreases body fat or fat distribution. Subjects/methods: In a randomized placebo-con...
Article
Full-text available
BACKGROUND: Vitamin K (VK)-dependent γ-glutamate carboxylation and serine phosphorylation activate matrix Gla protein (MGP) to a potent locally acting inhibitor of calcification. Nephrolithiasis represents a process of unwanted calcification associated with substantial mortality and high recurrence rates. We hypothesized that the risk of nephrolith...
Article
Full-text available
Matrix Gla Protein (MGP) is a strong vitamin K-dependent inhibitor of soft tissue calcification. We assessed the prevalence of functional vitamin K insufficiency, as derived from plasma desphospho-uncarboxylated MGP (dp-ucMGP), and investigated whether plasma dp-ucMGP is associated with all-cause and cardiovascular mortality in a large general popu...
Article
Full-text available
Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require anticoagulation therapy. Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used. VKAs induce profound deficiency of vitamin K, a key...
Article
Full-text available
Elastin is a unique protein providing deformability and resilience to dynamic tissues, such as arteries and lungs. It is an absolute basic requirement for circulation and respiration. Elastin can be degraded by elastases and has a high calcium affinity. Elastin calcification and elastin degradation are two pathological processes that impair elastin...
Article
Full-text available
Background: Recent studies showing an inverse association between estimated glomerular filtration rate (eGFR), a microvascular trait, and inactive desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) support the hypothesis that after vitamin K-dependent activation, matrix Gla protein (MGP) is renoprotective, but these were limited by their cros...
Article
Full-text available
Background/objectives: This study aims to investigate the reproducibility and relative validity of the Dutch food frequency questionnaire (FFQ), to estimate intake of dietary phylloquinone and menaquinones compared with 24-h dietary recalls (24HDRs) and plasma markers of vitamin K status. Subjects/methods: In a cross-sectional study among 63 men...
Poster
Full-text available
Introduction: Elastin is an essential protein in lungs and arteries. Chronic obstructive pulmonary disease (COPD) is associated with accelerated elastin degradation. The rate of elastin degradation –quantified with plasma desmosine levels– is a predictor of mortality in COPD. Elastin has high affinity for calcium. Consequently, elastin’s calcium co...
Article
Full-text available
Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiova...
Article
Both vitamins K and D are nutrients with pleiotropic functions in human tissues. The metabolic role of these vitamins overlaps considerably in calcium homeostasis. We analyzed their potential synergetic effect on arterial stiffness. In a cross-sectional study, we analyzed aortic pulse wave velocity (aPWV) in 1023 subjects from the Czech post-MONICA...
Article
Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K–dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (...
Article
Introduction: Vitamin K is a fat soluble vitamin and is required as a co-factor for the carboxylation of several proteins. Matrix gla-protein (MGP) requires vitamin K for its activation and is a potent vascular calcification inhibitor. High concentrations of dephosphorylated uncarboxylated MGP (dp-ucMGP) -a functional marker of vitamin K status- ar...
Article
Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vit...
Article
Background: Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular c...
Article
Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro bioactivity resulting in 2.5 a...
Chapter
Matrix Gla protein (MGP) is a vitamin K-dependent protein acting as an inhibitor of vascular calcification. Poor dietary vitamin K intake results in the formation of inactive MGP, also known as uncarboxylated MGP, which is set free in the blood stream where it is available for quantification by ELISA-based assays. In the healthy adult population, s...
Article
Objective: Vitamin K (VK) dependent carboxylation of matrix Gla protein (MGP) protects the macrocirculation against calcification. Whether glomerular filtration (GFR), a renal microvascular trait, is related to circulating desphospho-uncarboxylated MGP (dp-ucMGP) has not been explored before. We therefore investigated our hypothesis in our Flemish...
Patent
Full-text available
A new function of vitamin K is disclosed which results in the provision of methods of treatment, both therapeutic and non-therapeutic, as well as functional foods and pharmaceutical products comprising vitamin K for improving microvascular integrity and capillary structure and function, thus preventing, mitigating, counteracting or curing diseases...
Patent
Full-text available
The invention provides methods and compositions for treating or preventing skin cancer, in partic ular melanoma, parakeratosis, improving the skin integrity, the skin barrier function and/or decreasing skin ageing in a mammalian subject, preferably a human subject, the method comprising applying vitamin Kl, vitamin K2, Matrix Gla-Protein (MGP) or a...
Article
Vitamin-K-dependent carboxylation of matrix Gla protein (MGP) protects the macrocirculation against calcification. We recently reported in a multiethnic population study that the estimated glomerular filtration rate, a microvascular trait, decreased and the risk of chronic kidney disease increased with higher circulating levels of inactive dephosph...
Article
Background & aims: Vitamin K has been associated with various health outcomes, including non-fatal cardiovascular diseases (CVD) and cancer. However, little is known about the association between vitamin K intake and all-cause and cause specific mortality. This study aims to investigate the association between vitamin K intake and all-cause and ca...
Article
Recently, Kariminejad et al. (JID, 2014, 134:2331-8) reported thirteen patients with phenotypes typical of pseudoxanthoma elasticum (PXE)-like syndrome but with no coagulation abnormalities. The phenotypes were associated with a homozygous splice-site mutation in the GGCX gene that caused the deletion of exon 3 (GGCX-Δex3). Here, we characterized t...
Article
Full-text available
Background Cardiovascular calcifications can be prevented by vitamin K and are accelerated by vitamin K antagonists. These effects are believed to be mainly mediated by the vitamin K-dependent matrix Gla protein. Another vitamin K-dependent protein, Gas6, is also expressed in vascular smooth muscle cells (VSMC). In vitro Gas6 expression was shown t...
Article
Full-text available
Background/aims: Desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) is formed as a result of vitamin K insufficiency. The aim of this study was to investigate the association between plasma dp-ucMGP, kidney function and cardiovascular risk factors before and after 9-months substitution of vitamin K2 in non-dialysis patients with chronic kidne...