Overexpression of Insulin-Like Growth Factor-2 in Expanded Endothelial Progenitor Cells Improves Left Ventricular Function in Experimental Myocardial Infarction

Demetz, Gabi; Oostendorp, Robert A.J.; Boxberg, A Melanie; Sitz, Wibke; Farrell, Eliane; Steppich, Birgit; Steinsiek, Anna-Lena; Rudelius, Martina; Ott, Ilka

doi:10.1159/000479872

Cited by 8 publications

(5 citation statements)

References 24 publications

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“…Active components of EPC paracrine secretion facilitated the proliferation and migration of VECs, and these effects were associated with the expression of VEGF and IGF [49][50][51]. VEGF can promote reendothelialisation, inhibit neointimal hyperplasia, and play a crucial role in vascular repair [45].…”

Section: Discussionmentioning

confidence: 99%

The effect of endothelial progenitor cell transplantation on neointimal hyperplasia and reendothelialisation after balloon catheter injury in rat carotid arteries

et al. 2021

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Background Reendothelialisation is the natural pathway that inhibits neointimal hyperplasia and in-stent restenosis. Circulating endothelial progenitor cells (EPCs) derived from bone marrow (BM) might contribute to endothelial repair. However, the temporal and spatial distributions of reendothelialisation and neointimal hyperplasia after EPC transplantation in injured arteries are currently unclear. Methods A carotid balloon injury (BI) model was established in Sprague-Dawley rats, and PKH26-labelled BM-derived EPCs were transplanted after BI. The carotid arteries were harvested on the first, fourth, seventh, and 14th day post-injury and analysed via light-sheet fluorescence microscopy and pathological staining (n = 3). EPC and human umbilical vein endothelial cell culture supernatants were collected, and blood samples were collected before and after transplantation. The paracrine effects of VEGF, IGF-1, and TGF-β1 in cell culture supernatants and serum were analysed by enzyme-linked immunosorbent assay (n = 4). Results Transplanted EPCs labelled with PKH26 were attached to the injured luminal surface the first day after BI. In the sham operation group, the transplanted EPCs did not adhere to the luminal surface. From the fourth day after BI, the mean fluorescence intensity of PKH26 decreased significantly. However, reendothelialisation and inhibition of neointimal hyperplasia were significantly promoted by transplanted EPCs. The degree of reendothelialisation of the EPC7d and EPC14d groups was higher than that of the BI7d and BI14d groups, and the difference in neointimal hyperplasia was observed between the EPC14d and BI14d groups. The number of endothelial cells on the luminal surface of the EPC14d group was higher than that of the BI14d group. The number of infiltrated macrophages in the injured artery decreased in the EPC transplanted groups. Conclusions Transplanted EPCs had chemotactic enrichment and attached to the injured arterial luminal surface. Although decreasing significantly after the fourth day at the site of injury after transplantation, transplanted EPCs could still promote reendothelialisation and inhibit neointimal hyperplasia. The underlying mechanism is through paracrine cytokines and not differentiation into mature endothelial cells.

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Section: Discussionmentioning

confidence: 99%

The effect of endothelial progenitor cell transplantation on neointimal hyperplasia and reendothelialisation after balloon catheter injury in rat carotid arteries

et al. 2021

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“…The ability of adult human heart to generate new cardio myocytes and vascular endothelial cells is limited, thus failing heart could be repaired by bone marrow (BM)derived stem/progenitor cell-based cardiac regeneration after AMI [2][3][4]. Endothelial progenitor cells (EPCs) play vital roles in revascularization and tissue repairs [5].…”

Section: Introductionmentioning

confidence: 99%

Hyperlipidemia attenuates the mobilization of endothelial progenitor cells induced by acute myocardial ischemia via VEGF/eNOS/NO/MMP-9 pathway

Zhou

Xun

et al. 2022

Aging

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This study aims to explore the role of hyperlipidemia in the mobilization of bone marrow (BM) endothelial progenitor cells (EPCs) induced by acute myocardial ischemia (AMI). To establish the hyperlipidemia complicated with AMI (HL-AMI) model, SD rats were intragastrically administered the high-fat emulsion for 4 weeks. Then their left anterior descending arteries were ligated. Rats in each group were randomly subdivided into seven subgroups. During 1st ~ 7th day following AMI modeling, rats in 1st ~ 7th subgroups were selected to be phlebotomized from their celiac artery after being anesthetized by pentobarbitone in turn. The quantity of circulating EPCs (CEPCs) was detected by flow cytometry, the expression of VEGF, eNOS, NO, MMP-9 in myocardial tissue was analyzed by western blot, and their plasma level was assayed by ELISA. Dynamic curves were plotted using these data. Within 7 days following AMI, compared with the AMI rats, in the HL-AMI rats, the myocardial infarct size, the plasma activity of CK, CK-MB, and the collagen deposition all remained at the higher levels; meanwhile, these rats showed more significant decreases in the count of CEPCs, the plasma level of VEGF etc., and their expression in myocardial tissue (P < 0.05 or P < 0.01). Our study showed that hyperlipidemia may attenuate the mobilization of BM EPCs induced by AMI via VEGF/eNOS/NO/MMP-9 signal pathway, which might partly account for hyperlipidemia hampering the repairs of AMI-induced cardiac injury.

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“…Indeed, many studies have shown that insulin as a growth factor is essential for the proliferation of EPCs. 32,33 In this study, we showed an increase in the tube length and tubulogenesis score (as a hallmark of angiogenesis) in diabetic patients treated with insulin plus metformin. In contrast, we showed that metformin alone inhibited angiogenesis.…”

Section: Discussionmentioning

confidence: 59%

“…However, when these patients received insulin plus metformin, the proliferative rate of EPCs was again increased. Indeed, many studies have shown that insulin as a growth factor is essential for the proliferation of EPCs …”

Section: Discussionmentioning

confidence: 99%

Improved angiogenic activity of endothelial progenitor cell in diabetic patients treated with insulin plus metformin

Asadian

Alibabrdel

Daei

et al. 2018

J of Cellular Biochemistry

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Type 2 diabetes (T2DM) is associated with an increased vascular disease. Moreover, endothelial progenitor cell (EPC) function is impaired in diabetic patients. Decreased EPC number plays a critical role in reduced endothelial repair and development of the vascular disorder. To determine the effect of metformin and insulin plus metformin on functional activity of EPCs, 130 participants were divided into three groups (group 1: healthy control; group 2: metformin; group 3: insulin plus metformin). The concentration of EPCs in the circulation was first quantified. Thereafter, circulating EPCs (cEPCs) were harvested and the biological features of these cells including proliferative, clonogenicity, tubulogenic, and migratory properties were analyzed after expansion. The serum protein levels of some proangiogenic factors were also measured. Our results showed greater numbers of cEPCs in control and in diabetic patients treated with insulin plus metformin than in metformin‐treated patients. Insulin plus metformin therapy was associated with augmented proliferative, clonogenicity, migratory, and tubulogenic activity of cEPCs in patients with T2DM. Increased serum concentrations of angiogenic factors were also observed in patients treated with insulin plus metformin. Western blot analysis showed increased protein levels of pTie‐2/Tie2 and Pakt/AKT in cEPCs harvested from T2DM, treated with insulin metformin plus. This study showed that treatment with insulin plus metformin in diabetic patients is associated with increased mobilization of EPCs into the circulation, with potential beneficial effect in vascular protection in diabetic patients.

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Overexpression of Insulin-Like Growth Factor-2 in Expanded Endothelial Progenitor Cells Improves Left Ventricular Function in Experimental Myocardial Infarction

Cited by 8 publications

References 24 publications

The effect of endothelial progenitor cell transplantation on neointimal hyperplasia and reendothelialisation after balloon catheter injury in rat carotid arteries

The effect of endothelial progenitor cell transplantation on neointimal hyperplasia and reendothelialisation after balloon catheter injury in rat carotid arteries

Hyperlipidemia attenuates the mobilization of endothelial progenitor cells induced by acute myocardial ischemia via VEGF/eNOS/NO/MMP-9 pathway

Improved angiogenic activity of endothelial progenitor cell in diabetic patients treated with insulin plus metformin

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