Vitamin C promotes human endothelial cell growth via the ERK-signaling pathway

Ulrich‐Merzenich, G; Zeitler, H.; Panek, Darius; Bokemeyer, Dirk; Vetter, Hans

doi:10.1007/s00394-006-0636-5

Cited by 37 publications

(24 citation statements)

References 33 publications

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“…Finally, there was a significant increase in DNA content in the CP21+HUVECs and CP21+HUVECs:MSCs groups cultured in the presence of osteogenic supplements compared with the same groups cultured without. Dexamethasone has been shown to induce MSC proliferation 18,103 and ascorbic acid has been shown to promote endothelial cell proliferation, [104][105][106] which might account for this increase in DNA content. However, the additional cells did not appear to influence mineralization or vascularization potential.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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In vitro bone regeneration strategies that prime mesenchymal stem cells (MSCs) with chondrogenic factors, to mimic aspects of the endochondral ossification process, have been shown to promote mineralization and vascularization by MSCs both in vitro and when implanted in vivo. However, these approaches required the use of osteogenic supplements, namely dexamethasone, ascorbic acid, and b-glycerophosphate, none of which are endogenous mediators of bone formation in vivo. Rather MSCs, endothelial progenitor cells, and chondrocytes all reside in proximity within the cartilage template and might paracrineally regulate osteogenic differentiation. Thus, this study tests the hypothesis that an in vitro bone regeneration approach that mimics the cellular niche existing during endochondral ossification, through coculture of MSCs, endothelial cells, and chondrocytes, will obviate the need for extraneous osteogenic supplements and provide an alternative strategy to elicit osteogenic differentiation of MSCs and mineral production. The specific objectives of this study were to (1) mimic the cellular niche existing during endochondral ossification and (2) investigate whether osteogenic differentiation could be induced without the use of any external growth factors. To test the hypothesis, we evaluated the mineralization and vessel formation potential of (a) a novel methodology involving both chondrogenic priming and the coculture of human umbilical vein endothelial cells (HUVECs) and MSCs compared with (b) chondrogenic priming of MSCs alone, (c) addition of HUVECs to chondrogenically primed MSC aggregates, (d-f) the same experimental groups cultured in the presence of osteogenic supplements and (g) a noncoculture group cultured in the presence of osteogenic growth factors alone. Biochemical (DNA, alkaline phosphatase [ALP], calcium, CD31 + , vascular endothelial growth factor [VEGF]), histological (alcian blue, alizarin red), and immunohistological (CD31 + ) analyses were conducted to investigate osteogenic differentiation and vascularization at various time points (1, 2, and 3 weeks). The coculture methodology enhanced both osteogenesis and vasculogenesis compared with osteogenic differentiation alone, whereas osteogenic supplements inhibited the osteogenesis and vascularization (ALP, calcium, and VEGF) induced through coculture alone. Taken together, these results suggest that chondrogenic and vascular priming can obviate the need for osteogenic supplements to induce osteogenesis of human MSCs in vitro, while allowing for the formation of rudimentary vessels.

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Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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“…Hence, there is a great need to use alternative drugs in these medical devices to promote ECs, and inhibit SMCs, to prevent thrombosis and neointimal hyperplasia, respectively. Vitamin C (L-AA) has been shown to promote ECs22–24 and inhibit SMCs16,23,25 when orally administered or added directly to the cell cultures 15,16. Although vitamin C has such beneficial properties, to the best of our knowledge, it has not yet been used in stents or vascular grafts since the need to deliver a drug to encourage EC growth, and inhibit SMC growth, has arisen recently.…”

Section: Discussionmentioning

confidence: 99%

“…The typical plasma concentration of L-AA in humans ranges between 37 μM and 121 μM 22. A plasma concentration of ≥70 μM of L-AA has been recommended for preventing coronary artery disease 34.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of the effects of vitamin C, sirolimus, and paclitaxel on the growth of endothelial and smooth muscle cells for cardiovascular medical device applications

Kakade¹,

Mani²

2013

DDDT

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Antiproliferative drugs such as sirolimus (SIR) and paclitaxel (PAT) are currently released from stents and vascular grafts to inhibit the growth of smooth muscle cells (SMCs), thereby preventing neointimal hyperplasia. However, these drugs delay or impair the growth of endothelial cells (ECs) on implant surfaces causing late thrombosis. Hence, there is a need to use alternative drugs in these implants to encourage the growth of ECs and to inhibit the growth of SMCs. Vitamin C (L-ascorbic acid [L-AA]) is one such drug which has been shown to encourage EC growth and inhibit SMC growth when orally administered or added directly to the cell cultures. In this research, four sets of in vitro cell culture experiments were carried out to compare the effects of L-AA, SIR, and PAT on the growth of ECs and SMCs under similar conditions, and to compare the effects of different doses of L-AA to determine the optimal dose for promoting maximum EC growth and inhibiting SMC growth. The ECs and SMCs treated with different drugs were characterized for their viability and proliferation, and morphology using the quantitative resazurin assay (as well as qualitative fluorescence microscopy characterization) and phase contrast microscopy, respectively, for up to 7 days. Also, the phenotype of ECs was characterized using immunofluorescence microscopy. Both SIR and PAT significantly inhibited the EC growth while L-AA significantly encouraged EC growth even more than that of the controls with no drugs. Also, L-AA significantly inhibited SMC growth although the inhibitory effect was inferior to that of SIR and PAT. The L-AA dosage study demonstrated that 100 μg and 300 μg of L-AA showed maximum EC growth after 7 days when compared to other dosages (1 μg, 500 μg, and 1000 μg) of L-AA and controls investigated in this study. Also, the 100 μg and 300 μg L-AA doses significantly inhibited the SMC growth. Thus, this study demonstrates that L-AA is a promising drug for potential use in stents and vascular grafts, to promote their endothelialization and inhibit neointimal hyperplasia.

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“…Western blots were performed by standard procedures as described earlier (14). A minimum of five independent samples per group were evaluated.…”

Section: Western Blot Analysismentioning

confidence: 99%

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis

Abdel-Aziz

Schneider

Neuhuber

et al. 2015

Mol Med

Self Cite

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Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein-coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.

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Vitamin C promotes human endothelial cell growth via the ERK-signaling pathway

Cited by 37 publications

References 33 publications

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

A comparative study of the effects of vitamin C, sirolimus, and paclitaxel on the growth of endothelial and smooth muscle cells for cardiovascular medical device applications

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis

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