Vitamin D improves the angiogenic properties of endothelial progenitor cells

Grundmann, M; Haidar, Mauro Abi; Placzko, Susann; Niendorf, R.; Darashchonak, Natallia; Hubel, Carl A.; Versen‐Höynck, Frauke von

doi:10.1152/ajpcell.00030.2012

Cited by 134 publications

(133 citation statements)

References 59 publications

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“…13,[16][17][18][19][20][21][22] Moreover, there is a lack of consensus about the threshold of 25(OH)D at which the risk of PE is decreased. Given a strong biological rationale for a link between vitamin D metabolism and the physiopathology of PE through immunomodulation 16 and angiogenesis, 23 stronger epidemiologic evidence from studies with larger sample sizes and control for important confounding variables is needed.…”

Section: -Hydroxyvitamin D; Preeclampsia; Vitamin Dmentioning

confidence: 99%

Vitamin D status in early pregnancy and risk of preeclampsia

Achkar¹,

Dodds²,

Giguère³

et al. 2015

American Journal of Obstetrics and Gynecology

107

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OBJECTIVE-We sought to examine the association between maternal serum 25-hydroxyvitamin D (25[OH]D) concentration in early pregnancy and the subsequent diagnosis of preeclampsia (PE).STUDY DESIGN-This was a nested case-control study from 2 prospective Canadian cohorts conducted in Quebec City, Quebec, and Halifax, Nova Scotia, from 2002 through 2010. Participants were pregnant women (n=169 cases with PE and 1975 controls). Maternal serum was drawn <20 weeks of gestation, and 25(OH)D measurement was performed. Cases were ascertained from medical records. Logistic regression analysis was used to estimate adjusted odds ratios with 95% confidence intervals.RESULTS-Women who developed PE had a significantly lower 25(OH)D concentration at a mean gestational age of 14 weeks compared with women in the control group (mean ± SD 25[OH]D 47.2 ± 17.7 vs 52.3 ± 17.2 nmol/L, P < .0001). Women with 25(OH)D <30 nmol/L compared to those with at least 50 nmol/L had a greater risk of developing PE (adjusted odds ratio, 2.23; 95% confidence interval, 1.29-3.83) after adjustment for prepregnancy body mass index, maternal age, smoking, parity, season and year of blood collection, gestational week at blood collection, and cohort site. Exploratory analysis with cubic splines demonstrated a dose-response relationship between maternal 25(OH)D and risk of PE, up to levels around 50 nmol/L, where the association appeared to plateau. Canada, Feb. 12-15, 2014; and CONCLUSION-Maternal CIHR Author Manuscript CIHR Author ManuscriptCIHR Author Manuscript women of child-bearing age should be explored as a strategy for reducing PE and for promoting a healthier pregnancy. Keywords 25-hydroxyvitamin D; preeclampsia; vitamin DOne of the United Nations' Millennium Development Goals for maternal health is to reduce maternal mortality by three-quarters by 2015. 1 Hypertensive disorders of pregnancy, including preeclampsia (PE), are among the leading causes of maternal morbidity and mortality. 2 The clinical manifestations of PE are well described as elevated blood pressure and protein-uria, 3 yet the etiology and prevention of the syndrome remain unclear.Strategies to prevent PE include anti-platelet action of low-dose aspirin 4 Several epidemiologic studies have explored the association between vitamin D status and PE. In 2 of these studies, serum concentrations of 25(OH)D and 1,25-hydroxyvitamin D in early pregnancy were lower in women who subsequently developed PE. 13,16 Overall, however, the epidemiological evidence is conflicting and previous studies are limited by small sample sizes or the absence of adjustment for relevant confounders, such as season, smoking, or parity. 13,[16][17][18][19][20][21][22] Moreover, there is a lack of consensus about the threshold of 25(OH)D at which the risk of PE is decreased. Given a strong biological rationale for a link between vitamin D metabolism and the physiopathology of PE through immunomodulation 16 and angiogenesis, 23 stronger epidemiologic evidence from studies with larger sample sizes and ...

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Section: -Hydroxyvitamin D; Preeclampsia; Vitamin Dmentioning

confidence: 99%

Vitamin D status in early pregnancy and risk of preeclampsia

Achkar¹,

Dodds²,

Giguère³

et al. 2015

American Journal of Obstetrics and Gynecology

107

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“…ECFCs from cord blood were isolated as previously described (53). The culture medium (complete endothelial growth medium, EGM-2) was endothelial basal medium 2 (Lonza, Walkersville, MD) with 10% fetal calf serum (Biochrom AG, Berlin, Germany) and 1% penicillin/streptomycin (Biochrom AG) supplemented with EGM-2 SingleQuots Kit (Lonza).…”

Section: Isolation Of Ecfcs and Huvecsmentioning

confidence: 99%

“…Immunofluorescence and flow cytometry were used to confirm the ECFC phenotype as previously described (53). Purity of the HUVEC cultures was determined by flow cytometric analysis (Partec GmbH, Münster, Germany) using the fluorescein-isothiocyanate-conjugated monoclonal anti-human-endothelial cell antibody CD31 and the R-phycoerythrin-conjugated monoclonal anti-human-fibroblast antibody CD90 (clone WM59 and 5E10; Dako Cytomation GmbH, Hamburg, Germany).…”

Section: Isolation Of Ecfcs and Huvecsmentioning

confidence: 99%

Gestational diabetes induces alterations of sirtuins in fetal endothelial cells

et al. 2015

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Background: Gestational diabetes (GDM) has long-term consequences for the offspring. Sirtuins (SIRTs) are associated with vascular and metabolic functions. We studied the impact of GDM on SIRT activity and expression in fetal endothelial colony-forming cells (ECFCs) and human umbilical vein endothelial cells (HUVECs) from pregnancies complicated by GDM. Methods: ECFCs and HUVECs were isolated from cord and cord blood of 10 uncomplicated pregnancies (NPs) and 10 GDM pregnancies. Nicotinamidadenindinukleotid (NAD + ) concentration, SIRT1 and SIRT3 activity, transcription levels of SIRT1, SIRT3, and SIRT4, and protein levels of SIRT1, SIRT3, and SIRT4 were determined in vitro with or without SIRT activators resveratrol (RSV) and paeonol. results: Fetal ECFCs from GDM pregnancies showed a decreased NAD + concentration, reduced SIRT1 and SIRT3 activity, and lower transcription levels of SIRT1, SIRT3, and SIRT4. HUVECs from GDM pregnancies had decreased NAD + concentrations and transcription levels of SIRT1 and SIRT4. RSV markedly enhanced the expression and activity of SIRTs in ECFCs and HUVECs, while paeonol was active only in ECFCs. conclusion: A reduction of SIRT activity and expression in fetal endothelial cells provides potential mechanistic insights into the pathophysiology of long-term cardiovascular complications observed in the offspring of GDM pregnancies. SIRT activators can increase SIRT activity in ECFCs, which opens perspectives for new therapeutic targets. a dverse events during fetal life have been implicated to induce fetal programming, which can result in chronic diseases (1). Especially gestational diabetes (GDM) of the mother has been associated with cardiovascular disease, metabolic syndrome, and obesity during later life in the offspring (2,3). The pathophysiological processes responsible for these late complications are largely unknown.Sirtuins (SIRTs) are important regulators of aging and metabolic diseases (4,5). Mammalian SIRTs belong to the histone deacetylase class III family comprising seven members (SIRT1-7), which require Nicotinamidadenindinukleotid (NAD + ) for their enzymatic activity (6). SIRT1 downregulation has been observed in peripheral blood mononuclear cells of individuals with impaired glucose tolerance (7,8). SIRT1 is known to regulate vascular endothelial cell functions (9). Furthermore, in vitro and in vivo studies demonstrated that a reduction in the number of endothelial progenitor cells (EPCs) under hyperglycemia is associated with reduced SIRT1 levels and activity (8,10). Endothelial cells regulate vascular tone and are the first fetal cells exposed to maternal hyperglycemia.In recent years, it has become evident that SIRT1 is a key player of EPC dysfunction in insulin resistance and metabolic syndrome (7,10,11). Overexpression of endothelium-specific SIRT1 protects against endothelial dysfunction induced by a high-fat diet and hyperglycemia (12,13). Recently, resveratrol (RSV) and paeonol (2′-Hydroxy-4′-methoxyacetophenone) have been shown to activate SIRTs and thus c...

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“…Vitamin D3 promotes angiogenesis in endothelial cell cultures [238]. Atorvastatin, pravastatin and simvastatin have both anti-and pro-angiogenic activities depending on the dose, specific angiogenic stimulus, and angiogenesis mechanism in the specific disease local microenviroment [239,240].…”

Section: Therapeutic Potential Of Targeting Angiogenesismentioning

confidence: 99%

Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis

Girolamo

Coppola

Ribatti

et al. 2014

Acta Neuropathologica Communications

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Angiogenesis, the formation of new vessels, is found in Multiple Sclerosis (MS) demyelinating lesions following Vascular Endothelial Growth Factor (VEGF) release and the production of several other angiogenic molecules. The increased energy demand of inflammatory cuffs and damaged neural cells explains the strong angiogenic response in plaques and surrounding white matter. An angiogenic response has also been documented in an experimental model of MS, experimental allergic encephalomyelitis (EAE), where blood-brain barrier disruption and vascular remodelling appeared in a pre-symptomatic disease phase. In both MS and EAE, VEGF acts as a pro-inflammatory factor in the early phase but its reduced responsivity in the late phase can disrupt neuroregenerative attempts, since VEGF naturally enhances neuron resistance to injury and regulates neural progenitor proliferation, migration, differentiation and oligodendrocyte precursor cell (OPC) survival and migration to demyelinated lesions. Angiogenesis, neurogenesis and oligodendroglia maturation are closely intertwined in the neurovascular niches of the subventricular zone, one of the preferential locations of inflammatory lesions in MS, and in all the other temporary vascular niches where the mutual fostering of angiogenesis and OPC maturation occurs. Angiogenesis, induced either by CNS inflammation or by hypoxic stimuli related to neurovascular uncoupling, appears to be ineffective in chronic MS due to a counterbalancing effect of vasoconstrictive mechanisms determined by the reduced axonal activity, astrocyte dysfunction, microglia secretion of free radical species and mitochondrial abnormalities. Thus, angiogenesis, that supplies several trophic factors, should be promoted in therapeutic neuroregeneration efforts to combat the progressive, degenerative phase of MS.

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Vitamin D improves the angiogenic properties of endothelial progenitor cells

Cited by 134 publications

References 59 publications

Vitamin D status in early pregnancy and risk of preeclampsia

Vitamin D status in early pregnancy and risk of preeclampsia

Gestational diabetes induces alterations of sirtuins in fetal endothelial cells

Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis

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