Inhibition of Notch rescues the angiogenic potential impaired by cardiovascular risk factors in epicardial adipose stem cells

Béjar, Maria Teresa; Ferrer-Lorente, Raquel; Peña, Esther; Badimon, Lina

doi:10.1096/fj.201600204r

Cited by 16 publications

(7 citation statements)

References 49 publications

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“…To understand the functional effect of differences in transcriptional expression between MSCs originating from IP and NU tissue, a matrigel-based angiotube formation assay that reflects the early stages of angiogenesis was performed [ 51 , 52 ], using conditioned IP- and NU-MSC growth media. Some angiogenesis was observed using unconditioned MSC growth media; therefore, this was used as a baseline and the contribution of MSC conditioning was standardised against this.…”

Section: Resultsmentioning

confidence: 99%

“…MSCs originating from IP and NU tissue were seeded in cell culture flasks (Corning Inc., New York, NY, USA) and incubated under standard conditions in MSC growth media (StemMACS Media). At 80% confluence, supernatant was removed and new MSC growth media was added, as previously described [51]. Following a further 72 h incubation, MSC conditioned media was centrifuged at 300× g for 10 min to eliminate dead cells and debris, and the supernatant was then frozen at −80 • C until use.…”

Section: In Vitro Angiogenesismentioning

confidence: 99%

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Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments

Cuthbert

Jones

Sanjurjo‐Rodríguez

et al. 2020

JCM

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Background: The biological mechanisms that contribute to atrophic long bone non-union are poorly understood. Multipotential mesenchymal stromal cells (MSCs) are key contributors to bone formation and are recognised as important mediators of blood vessel formation. This study examines the role of MSCs in tissue formation at the site of atrophic non-union. Materials and Methods: Tissue and MSCs from non-union sites (n = 20) and induced periosteal (IP) membrane formed following the Masquelet bone reconstruction technique (n = 15) or bone marrow (n = 8) were compared. MSC content, differentiation, and influence on angiogenesis were measured in vitro. Cell content and vasculature measurements were performed by flow cytometry and histology, and gene expression was measured by quantitative polymerase chain reaction (qPCR). Results: MSCs from non-union sites had comparable differentiation potential to bone marrow MSCs. Compared with induced periosteum, non-union tissue contained similar proportion of colony-forming cells, but a greater proportion of pericytes (p = 0.036), and endothelial cells (p = 0.016) and blood vessels were more numerous (p = 0.001) with smaller luminal diameter (p = 0.046). MSCs showed marked differences in angiogenic transcripts depending on the source, and those from induced periosteum, but not non-union tissue, inhibited early stages of in vitro angiogenesis. Conclusions: In vitro, non-union site derived MSCs have no impairment of differentiation capacity, but they differ from IP-derived MSCs in mediating angiogenesis. Local MSCs may thus be strongly implicated in the formation of the immature vascular network at the non-union site. Attention should be given to their angiogenic support profile when selecting MSCs for regenerative therapy.

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Section: Resultsmentioning

confidence: 99%

Section: In Vitro Angiogenesismentioning

confidence: 99%

Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments

Cuthbert

Jones

Sanjurjo‐Rodríguez

et al. 2020

JCM

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“…Few studies have analyzed the presence and function of heart adipose tissue-derived stem cells, neither in animal [45, 46] nor in human [19] models, and in none of them, their angiogenic potential has been analyzed and compared. Previous studies in our group have shown how ASCs derived from the subcutaneous adipose tissue, independently of the BMI, have no ability to form tubes in a Matrigel-based experiment [11], but here, we demonstrate for the first time that both mASCs and pASCs, when seeded in a 3D Matrigel surface and cultured with EGM-2 medium, are able to form capillary-like ring structures, independently of cardiac fat location and of atherosclerosis severity in the LAD indicating a proangiogenic function.…”

Section: Discussionmentioning

confidence: 99%

Stem cells from human cardiac adipose tissue depots show different gene expression and functional capacities

et al. 2019

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BackgroundThe composition and function of the adipose tissue covering the heart are poorly known. In this study, we have investigated the epicardial adipose tissue (EAT) covering the cardiac ventricular muscle and the EAT covering the left anterior descending artery (LAD) on the human heart, to identify their resident stem cell functional activity.MethodsEAT covering the cardiac ventricular muscle was isolated from the apex (avoiding areas irrigated by major vessels) of the heart (ventricular myocardium adipose tissue (VMAT)) and from the area covering the epicardial arterial sulcus of the LAD (PVAT) in human hearts excised during heart transplant surgery. Adipose stem cells (ASCs) from both adipose tissue depots were immediately isolated and phenotypically characterized by flow cytometry. The different behavior of these ASCs and their released secretome microvesicles (MVs) were investigated by molecular and cellular analysis.ResultsASCs from both VMAT (mASCs) and the PVAT (pASCs) were characterized by the expression of CD105, CD44, CD29, CD90, and CD73. The angiogenic-related genes VEGFA, COL18A1, and TF, as well as the miRNA126-3p and miRNA145-5p, were analyzed in both ASC types. Both ASCs were functionally able to form tube-like structures in three-dimensional basement membrane substrates. Interestingly, pASCs showed a higher level of expression of VEGFA and reduced level of COL18A1 than mASCs. Furthermore, MVs released by mASCs significantly induced human microvascular endothelial cell migration.ConclusionOur study indicates for the first time that the resident ASCs in human epicardial adipose tissue display a depot-specific angiogenic function. Additionally, we have demonstrated that resident stem cells are able to regulate microvascular endothelial cell function by the release of MVs.

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“…Moreover, we have described that ASCs, in both humans and in rats, are functionally affected by cardiovascular risk factors (CVRFs) [ 22 , 27 , 28 ]. Particularly epicardial ASCs in animals with CVRFs lose their original angiogenic potential [ 29 ] or SAT-ASCs are committed to the adipogenic lineage, while their proliferation rate and proangiogenic potential are impaired in patients with obesity [ 22 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Risk Factors and Differential Transcriptomic Profile of the Subcutaneous and Visceral Adipose Tissue and Their Resident Stem Cells

Arderiu

Lambert

Ballesta

et al. 2020

Cells

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Background: The increase in the incidence of obesity and obesity-related cardiovascular risk factors (CVRFs) over the last decades has brought attention on adipose tissue (AT) pathobiology. The expansion of AT is associated with the development of new vasculature needed to perfuse the tissue; however, not all fat depots have the same ability to induce angiogenesis that requires recruitment of their own endothelial cells. In this study we have investigated the effect of different CVRFs, on the angiogenic capacity of the subcutaneous (SAT) and visceral (VAT) adipose tissue and on the function of their mesenchymal cell reservoir. Methods: A transcriptomic approach was used to compare the different angiogenic and inflammatory profiles of the subcutaneous and visceral fat depots from individuals with obesity, as well as their resident stem cells (ASCs). Influence of other risk factors on fat composition was also measured. Finally, the microvesicles (MVs) released by ASCs were isolated and their regenerative potential analyzed by molecular and cellular methodologies. Results: Obesity decreases the angiogenic capacity of AT. There are differences between SAT and VAT; from the 21 angiogenic-related genes analyzed, only three were decreased in SAT compared with those decreased in VAT. ASCs isolated from both fat depots showed significant differences; there was a significant up-regulation of the VEGF-pathway on visceral derived ASCs. ASCs release MVs that stimulate endothelial cell migration and angiogenic capacity. Conclusions: In patients with obesity, SAT expresses a greater number of angiogenic molecules than VAT, independent of the presence of other CVRFs.

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Inhibition of Notch rescues the angiogenic potential impaired by cardiovascular risk factors in epicardial adipose stem cells

Cited by 16 publications

References 49 publications

Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments

Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments

Stem cells from human cardiac adipose tissue depots show different gene expression and functional capacities

Cardiovascular Risk Factors and Differential Transcriptomic Profile of the Subcutaneous and Visceral Adipose Tissue and Their Resident Stem Cells

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