Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice

Hu, Yanhua; Zhang, Zhongyi; Torsney, Evelyn; Afzal, Ali R.; Davison, Fergus; Metzler, Bernhard; Xu, Qingbo

doi:10.1172/jci19628

Cited by 590 publications

(435 citation statements)

References 53 publications

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“…The vessel wall resident Sca1 + ‐VPCs can differentiate toward both EC and smooth muscle cell (SMC) lineages 17, 34. When embryonic stem cells differentiate into SMCs, the Hdac7 transcript variant 2 undergoes further splicing, leading to the incorporation of 7A into the far N‐terminal end of the HDAC7 protein 18.…”

Section: Resultsmentioning

confidence: 99%

“…Vascular tissue‐resident stem cells have been discovered to display the capacity to differentiate into vascular cell lineages, which may contribute to the regenerative process 34. More specifically, the adventitial resident VPCs play a major role in the repair of the injured endothelium via migration toward the endothelium and differentiation into an EC lineage 5, 6…”

Section: Discussionmentioning

confidence: 99%

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Histone Deacetylase 7‐Derived Peptides Play a Vital Role in Vascular Repair and Regeneration

et al. 2018

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Cardiovascular disease is a leading cause of morbidity and mortality globally. Accumulating evidence indicates that local resident stem/progenitor cells play an important role in vascular regeneration. Recently, it is demonstrated that a histone deacetylase 7‐derived 7‐amino acid peptide (7A, MHSPGAD) is critical in modulating the mobilization and orientated differentiation of these stem/progenitor cells. Here, its therapeutic efficacy in vascular repair and regeneration is evaluated. In vitro functional analyses reveal that the 7A peptide, in particular phosphorylated 7A (7Ap, MH[pSer]PGAD), could increase stem cell antigen‐1 positive (Sca1+) vascular progenitor cell (VPC) migration and differentiation toward an endothelial cell lineage. Furthermore, local delivery of 7A as well as 7Ap could enhance angiogenesis and ameliorate vascular injury in ischaemic tissues; these findings are confirmed in a femoral artery injury model and a hindlimb ischaemia model, respectively. Importantly, sustained delivery of 7A, especially 7Ap, from tissue‐engineered vascular grafts could attract Sca1+‐VPC cells into the grafts, contributing to endothelialization and intima/media formation in the vascular graft. These results suggest that this novel type of peptides has great translational potential in vascular regenerative medicine.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase 7‐Derived Peptides Play a Vital Role in Vascular Repair and Regeneration

et al. 2018

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“…The internal validity of our investigation was ensured at several key levels, with the randomized treatment groups being properly balanced for basal measurements, receiving identical care and assessment, and having similarly low levels of participant loss at final follow‐up. Furthermore, we used the ARRIVE consensus checklist to certify the proper and complete reporting of research data 15. Results obtained in swine were critically compared with previous studies conducted by us in mice (Table 7), to draw more definitive conclusions about the safety and efficacy of this new cell therapy product.…”

Section: Discussionmentioning

confidence: 99%

“…Different mesenchymal cell populations have been isolated from the adventitial layer of murine and human vessels 9, 10, 11, 12, 13, 14, 15. In a seminal study, we discovered the presence of CD133 + /CD34 + /KDR + cells endowed with potent vasculogenic activity in the human fetal aorta 14.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction

Alvino

Fernández‐Jiménez

Rodriguez‐Arabaolaza

et al. 2018

JAHA

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BackgroundTransplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model.Methods and ResultsWe performed a blind, randomized, placebo‐controlled APC therapy trial in a swine model of reperfused myocardial infarction. A first study used human APCs (hAPCs) from patients undergoing coronary artery bypass graft surgery. A second study used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction as assessed by cardiac magnetic resonance imaging and (2) myocardial vascularization and fibrosis as determined by immunohistochemistry. Transplantation of hAPCs reduced fibrosis but failed to improve the other efficacy end points. Incompatibility of the xenogeneic model was suggested by the occurrence of a cytotoxic response following in vitro challenge of hAPCs with swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted hearts. We next considered sAPCs as an alternative. Flow cytometry, immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary density and fibrosis but did not improve cardiac magnetic resonance imaging indices of contractility. Transplanted cells were detected in the border zone.ConclusionsImmunologic barriers limit the applicability of a xenogeneic swine model to assess hAPC efficacy. On the other hand, we newly show that transplantation of allogeneic sAPCs is feasible, safe, and immunologically acceptable. The approach induces proangiogenic and antifibrotic benefits, though these effects were not enough to result in functional improvements.

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“…Recently, a new type of SCs was identified in the murine arterial media, named multipotent vascular SCs, which could differentiate into neural cells and MSC‐like cells and subsequently differentiate into SMCs 91. In addition, abundant progenitor/SCs expressing Sca‐1 have been identified in the adventitia, which may contribute to endothelial regeneration and smooth muscle accumulation in the neointimal lesions 92.…”

Section: Pm and Stem Cellsmentioning

confidence: 99%

Ambient particulate matter exposure and cardiovascular diseases: a focus on progenitor and stem cells

Cui

Sun

Liu

2016

J Cellular Molecular Medi

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Air pollution is a major challenge to public health. Ambient fine particulate matter (PM) is the key component for air pollution, and associated with significant mortality. The majority of the mortality following PM exposure is related to cardiovascular diseases. However, the mechanisms for the adverse effects of PM exposure on cardiovascular system remain largely unknown and under active investigation. Endothelial dysfunction or injury is considered one of the major factors that contribute to the development of cardiovascular diseases such as atherosclerosis and coronary heart disease. Endothelial progenitor cells (EPCs) play a critical role in maintaining the structural and functional integrity of vasculature. Particulate matter exposure significantly suppressed the number and function of EPCs in animals and humans. However, the mechanisms for the detrimental effects of PM on EPCs remain to be fully defined. One of the important mechanisms might be related to increased level of reactive oxygen species (ROS) and inflammation. Bone marrow (BM) is a major source of EPCs. Thus, the number and function of EPCs could be intimately associated with the population and functional status of stem cells (SCs) in the BM. Bone marrow stem cells and other SCs have the potential for cardiovascular regeneration and repair. The present review is focused on summarizing the detrimental effects of PM exposure on EPCs and SCs, and potential mechanisms including ROS formation as well as clinical implications.

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Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice

Abstract: Nonstandard abbreviations used: smooth muscle (SM); smooth muscle cell (SMC); stage-specific embryonic antigen-1 (SSEA-1); stem cell antigen-1 (Sca-1).

Cited by 590 publications

References 53 publications

Histone Deacetylase 7‐Derived Peptides Play a Vital Role in Vascular Repair and Regeneration

Histone Deacetylase 7‐Derived Peptides Play a Vital Role in Vascular Repair and Regeneration

Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction

Ambient particulate matter exposure and cardiovascular diseases: a focus on progenitor and stem cells

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