Endothelial Progenitor Cell-Based Therapy for Pulmonary Arterial Hypertension

Jin, Yang; Pan, Yijie; Zhao, You Yang; Wang, Xing Xiang

doi:10.3727/096368912x659899

Cited by 20 publications

(12 citation statements)

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“…Meanwhile, the elevated level of TNF-α may represent a hostile microenvironment which may induce EPCs differentiation into abberant cells [33]. So drug regimen before or in combination with cell transplantation may be a promising strategy for the future EPC therapy for cardiovascular diseases [33]. The purpose of this study was to examine the effect of Tan IIA on expression of adhesion molecules in TNF-α-induced EPCs.…”

Section: Discussionmentioning

confidence: 99%

“…TNF-α was found to reduce proliferation, adhesion, migration and tube formation ability of EPCs [32]. Meanwhile, the elevated level of TNF-α may represent a hostile microenvironment which may induce EPCs differentiation into abberant cells [33]. So drug regimen before or in combination with cell transplantation may be a promising strategy for the future EPC therapy for cardiovascular diseases [33].…”

Section: Discussionmentioning

confidence: 99%

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Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

Yang

Pan

et al. 2016

Cell Physiol Biochem

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Background/Aims: Tanshinone IIA (Tan IIA) is effective in the treatment of inflammation and atherosclerosis. The adhesion of inflammatory cells to vascular endothelium plays important role in atherogenic processes. This study examined the effects of Tan IIA on expression of adhesion molecules in tumor necrosis factor-α (TNF-α)-induced endothelial progenitor cells (EPCs). Methods: EPCs were pretreated with Tan IIA and stimulated with TNF-α. Mononuclear cell (MNC) adhesion assay was performed to assess the effects of Tan IIA on TNF-α-induced MNC adhesion. Expression of vascular cell adhesion molecule-1 (VCAM-1)/intracellular adhesion molecule-1 (ICAM-1) and activation of Nuclear factor κB (NF-κB) signaling pathway were measured. Results: The results showed that the adhesion of MNCs to TNF-α-induced EPCs and expression of VCAM-1/ICAM-1 in EPCs were promoted by TNF-α, which were reduced by Tan IIA. TNF-α increased the amount of phosphorylation of NF-κB, IκB-α and IKKα/β in cytosolic fractions and NF-κB p65 in nucleus, while Tan IIA reduced its amount. Conclusion: This study demonstrated a novel mechanism for the anti-inflammatory/anti-atherosclerotic activity of Tan IIA, which may involve down-regulation of VCAM-1 and ICAM-1 through partial blockage of TNF-α-induced NF-κB activation and IκB-α phosphorylation by the inhibition of IKKα/β pathway in EPCs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

Yang

Pan

et al. 2016

Cell Physiol Biochem

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“…In the recently concluded pulmonary hypertension and angiogenic cell therapy (PHACeT) trial, endothelial nitric oxide synthase (eNOS)‐transfected eEPCs were systemically administered to patients with pulmonary arterial hypertension (PAH) [54]. EPC injections have previously been shown to stimulate endothelial repair and ameliorate PAH conditions [55], and in the PHACeT trial, the use of eNOS‐augmented eEPCs was expected to have increased vasodilatory and vasoregenerative effects. Modest improvements in quality of life measures were observed in patients following treatment, although these could not be sustained, and the group was unable to ascertain the safety or efficacy of this approach.…”

Section: Clinical Application Of Epcs In Regenerative Medicinementioning

confidence: 99%

Concise Review: Endothelial Progenitor Cells in Regenerative Medicine: Applications and Challenges

Chong

Chan

2016

Stem Cells Translational Medicine

174

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Endothelial progenitor cells (EPCs) are currently being studied as candidate cell sources for revascularization strategies. Significant advances have been made in understanding the biology of EPCs, and preclinical studies have demonstrated the vasculogenic, angiogenic, and beneficial paracrine effects of transplanted EPCs in the treatment of ischemic diseases. Despite these promising results, widespread clinical acceptance of EPCs for clinical therapies remains hampered by several challenges. The present study provides a concise summary of the different EPC populations being studied for ischemic therapies and their known roles in the healing of ischemic tissues. The challenges and issues surrounding the use of EPCs and the current strategies being developed to improve the harvest efficiency and functionality of EPCs for application in regenerative medicine are discussed. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:530-538 SIGNIFICANCEEndothelial progenitor cells (EPCs) have immense clinical value for cardiovascular therapies. The present study provides a concise description of the EPC subpopulations being evaluated for clinical applications. The current major lines of investigation involving preclinical and clinical evaluations of EPCs are discussed, and significant gaps limiting the translation of EPCs are highlighted. The present report could be useful for clinicians and clinical researchers with interests in ischemic therapy and for basic scientists working in the related fields of tissue engineering and regenerative medicine.

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“…These cells do not express markers which are characteristic of mature endothelial cells and are not involved in lumen formation ( 7 , 8 ). Increasing evidence has suggested that EPCs have a role in the endothelial repair process through differentiation into mature ECs and the release of protective paracrine factors, including vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) ( 9 ). Therefore, improving EPC number and function through pharmacological modulation may be a novel strategy for atherosclerosis prevention and treatment.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of tanshinone IIA on endothelial progenitor cells injured by tumor necrosis factor-α

Wang

Yang

Pan

et al. 2015

Molecular Medicine Reports

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Tanshinone IIA (Tan IIA) is a Traditional Chinese Medicine commonly used in Asian and Western countries for the prevention and treatment of cardiovascular disorders, such as atherosclerosis. Endothelial dysfunction and associated inflammatory processes have a critical role in the development of atherosclerosis. Endothelial progenitor cells (EPCs) have been demonstrated to be involved in certain aspects of the endothelial repair process. The present study aimed to investigate the putative protective effects of Tan IIA on EPCs injured by tumor necrosis factor-α (TNF-α). The potential effects of Tan IIA on TNF-α-stimulated EPC proliferation, migration, adhesion, in vitro tube formation ability and paracrine activity were investigated in the current study. The results indicated that TNF-α impaired EPC proliferation, migration, adhesion capacity and vasculogenesis ability in vitro as well as promoted EPC secretion of inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and soluble CD40 ligand (sCD40L). However, Tan IIA was able to reverse these effects. In conclusion, these findings demonstrated that Tan IIA may have the potential to protect EPCs against damage induced by TNF-α. Therefore, these results may provide evidence for the pharmacological basis of Tan IIA and its potential use in the prevention and treatment of early atherosclerosis associated with EPC and endothelial damage.

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Endothelial Progenitor Cell-Based Therapy for Pulmonary Arterial Hypertension

Cited by 20 publications

References 100 publications

Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

Concise Review: Endothelial Progenitor Cells in Regenerative Medicine: Applications and Challenges

Protective effects of tanshinone IIA on endothelial progenitor cells injured by tumor necrosis factor-α

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