Abstract 13054: Thymosin Beta-4-Treated Endothelial Progenitor Cells Improve Cardiac Function and Vasculogenesis in Diabetic Obese Rats with Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Poay Sian S Lee ◽  
Lei Ye ◽  
Yei-Tsung Chen ◽  
Eric Yin Hao Khoo ◽  
Tiong Cheng Yeo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Endothelial Progenitor ◽  
Thymosin Beta 4 ◽  
Zdf Rats ◽  
Angiogenic Cytokines

Introduction: Diabetes and obesity are associated with endothelial dysfunction and may impair circulating endothelial progenitor cells (EPCs). Thymosin beta-4 (Tβ4), a novel peptide with angiogenic properties, may improve EPC number and function. Hypothesis: We aim to transplant allogenic Tβ4-treated EPCs in Zucker Diabetic Fatty (ZDF) rats with myocardial infarction (MI) and hypothesize that Tβ4-treated EPCs may improve cardiac function, vasculogenesis and upregulate angiogenic cytokines and genes, compared to non-treated EPCs and controls. Methods: The left anterior descending coronary artery was permanently ligated to induce experimental MI on ZDF rats (n=19), divided into MI+saline(n=6); MI+EPCs (n=6) and MI+Tβ4-treated EPCs (n=7). Peripheral blood mononuclear cells were harvested from ZDF rats and isolated using Ficoll density gradient centrifugation and grown on fibronectin-coated plates. EPCs were treated with Tβ4 (1μg/mL) on day 7. At day 10, allogenic EPCs were harvested and transplanted into the peri-infarcted myocardium. Echocardiographic examination including strain assessment, immunohistological assessments and assays of angiogenic cytokines were performed 6 weeks after surgery. Results: Left ventricular (LV) ejection fraction was improved in Tβ4-treated EPCs (72.0±7.6%) and non-treated EPCs rats (80.5±5.9%) compared to control MI rats (64.8±19.7%) (P=0.04). Similar improvement was observed in LV radial strain rate in rats with Tβ4-treated EPCs (-7.22±1.24 1/s) and non-treated EPCs (-6.67±2.66 1/s) compared to MI only (-4.08±3.75 1/s) (P<0.01). Vascular density (CD31) and c-kit density (CD117) were significantly upregulated in Tβ4-treated EPCs rats compared to MI (P=0.03; P=0.005 respectively) and non-treated EPCs rats (P=0.04; P=0.04 respectively). Angiogenic cytokines of PDGF-BB, IGF-1 and VEGF levels were increased by 1.5 fold in Tβ4-treated EPCs and supported by similar trend in mRNA levels compared to non-treated EPCs (P<0.01). Conclusions: ZDF rats with Tβ4-treated EPCs had significant improvement in cardiac function, increased vasculogenesis and upregulation of angiogenic cytokines and genes. This suggests that Tβ4 may be beneficial in enhancing efficacy of EPCs in cell-based therapies.

scholarly journals Transplantation of Endothelial Progenitor Cells in the Treatment of Coronary Artery Microembolism in Rats

2020 ◽  
Vol 29 ◽  
pp. 096368972091268
Author(s):  
Yajun Xue ◽  
Boda Zhou ◽  
Jian Wu ◽  
Guobin Miao ◽  
Kun Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Low Dose ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Endothelial Progenitor ◽  
Ventricular Ejection Fraction

As the impairment of myocardial microenvironments due to coronary microembolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME. Low- (2 × 105) and high- (2 × 106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood-clots into the left ventricle. Echocardiograph was examined before and 1, 7, and 28 days after EPC transplantation; serum cardiac troponin I (cTNI), von Willebrand factor (vWF), and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and vascular endothelial growth factor (VEGF), vWF, and basic fibroblast growth factor (bFGF) expression were examined one day after EPC transplantation. After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by left ventricular ejection fraction significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a proangiogenic, antifibroblast, antifibrosis, and antinecrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.

Abstract 5759: Intramyocardial Application Of Erythropoietin And Expanded Endothelial Progenitor Cells Improve Regional Left Ventricular Function After Induced Myocardial Infarction In Rats

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Andreas Stein ◽  
Antti Saraste ◽  
Marcus Makowski ◽  
Sandra Kühnel ◽  
Elisabeth Weidl ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Function ◽  
Progenitor Cells ◽  
Ventricular Function ◽  
Endothelial Progenitor Cells ◽  
Left Ventricular ◽  
Border Zone ◽  
Control Group ◽  
Endothelial Progenitor ◽  
Regional Left Ventricular Function

Background : Experimental studies showed that application of expanded endothelial progenitor cells (eEPC) after myocardial infarction improves cardiac function by enhancing vasculogenesis and by paracrine effects. Erythropoietin beta (EPO) could further improve myocardial function through its anti-apoptotic properties. Methods : Acute myocardial ischemia was induced by ligation of the left anterior descending coronary artery of 23 male athymic nude rats and reperfusion was initiated after 30 minutes. Either 1×10^6 eEPC alone (n=8), 50 IU erythropoietin beta alone (n=7) or eEPC and EPO (n=8) were injected intramyocardially into the border zone of the ischemic area. eEPC were attained by expanding CD34+ cells isolated from cord blood in endothelial medium for 6 –10 passages. A control group did not receive cells or erythropoietin (n=5). After 4 weeks global and regional left ventricular function was measured by MRI in 2- and 4-chamber long-axis series (Philips Achieva MR Scanner). Immunhistology was used to determine vessel densitiy (SMC actin) and infiltrating monocytes (CD68) after 3 days (n=15) and 4 weeks. Results : Global left ventricular function after 4 weeks was higher in rats that received eEPC alone (58±3%, p=.02) or eEPC + EPO (58±6%, p=.01) compared to the control group (54±5%). No changes were found for rats treated with EPO alone (52±4%). Analysis of the regional wall movement showed a further improvement of the movement of the antero-lateral segments only in rats that obtained eEPC + EPO. The number of CD68+ mononuclear cells after 3 days was highest in rats that were treated with eEPC + EPO. This was associated with an increase in vessel density after 4 weeks. In vitro experiments revealed a dose-dependent inhibition of apoptosis by EPO in eEPC. Conclusion: Intramyocardial transplantation of eEPCs + EPO further improved anterolateral wall motion as compared to EPC alone. Improved eEPC survival, alterations in local inflammatory responses and neovascularization may contribute to this effect.

Influence of Hypoxia Inducible Factor-1α of Endothelial Progenitor Cells on Left Ventricular Function in Experimental Myocardial Infarction

2022 ◽  
Vol 12 (4) ◽  
pp. 731-738
Author(s):  
Zhitang Chang ◽  
Guotai Sheng ◽  
Yizhong Zhou ◽  
Zhiyong Wu ◽  
Guobo Xie ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cell Death ◽  
Left Ventricle ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Hypoxia Inducible Factor ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Low Oxygen ◽  
Endothelial Progenitor

Based on the promotion of myocardial activity via endothelial progenitor cells (EPCs) subsequent to acute myocardial infarction (AMI), our research was designed to explore the influence of excessive HIF-1α expression in expanded EPCs (eEPCs) on promotion of the activity of left ventricle subsequent to MI. Isolation of EPCs from cord blood was performed before transduction with the help of retroviral vector with or without HIF-1α expression. Transplantation was performed subsequent to ligation of the left anterior descending coronary artery in mice. Ejection fraction (EF) of left ventricle was promoted via transplantation after 2 weeks. Excessive HIF-1α expression enhanced EF of left ventricle and decreased the extent of MI. It was revealed via functional studies that excessive HIF-1α expression enhanced proliferation of EPCs triggered by low oxygen concentration and suppressed cell death in the region of infarction. Moreover, markers of endothelium CD31, VEGF, and eNOS were upregulated. Transplantation of eEPCs with excessive HIF-1α expression in AMI can promote myocardial activities by increasing differentiation, generation of vessels, proliferation of eEPCs, and suppressing cell death. The above findings propose that regulation of EPCs via HIF-1α enhances the activity as well as mobilization of EPCs, indicating that reinforcement of expression of HIF-1α is beneficial for coronary heart disease.

Abstract 5731: An Increase of Intrinsic Endothelial Progenitor Cells after Acute Myocardial Infarction was Associated with Spontaneous Neovascularization but not with Improvement of Left Ventricula Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Motoo Date ◽  
Hiroshi Ito ◽  
Katsuomi Iwakura ◽  
Atsunori Okamura ◽  
Yasushi Koyama ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Left Ventricular ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Infarct Zone ◽  
Endothelial Progenitor ◽  
Ventricular Ejection Fraction

Endothelial progenitor cells (EPC) increase after acute myocardial infarction and may contribute to neovascularization in the infarct zone. The aim of this study was to elucidate the relation of EPC release to recovery of microvascualr and myocardial function. Eighteen patients with acute myocardial infarction (AMI) undergoing primary PCI within 12 hours after onset were enrolled. CD34 + cells were counted at days-1, 7 and 14 as an index of EPC. We performed triggered end-systolic myocardial contrast echocardiography (MCE) at every 6 cardiac cycles with continuous infusion of Levovist at days-2 and 14. We performed left ventriculography 6 months later to calculate left ventricular ejection fraction (LVEF) and end-diastolic volume index (LVEDVI). The number of EPC at day-7 was significantly higher than that at day-1 (1.29+/−0.75 vs. 2.10+/−1.25/micL, p<0.001). It was correlated with myocardial blood volume (MBV), that implies microvascular integrity, at day-14 measured from MCE image (r 2 =0.652, p<0.005) and with an increase in MBV from day-1 to day-7 (r 2 =0.533, p<0.005). To evaluate the correlation between EPC and LV function, we divided patients into two groups according to the number of EPC at day-7. LVEF and LVEDVI were comparable between the higher number of EPC and the lower number of EPC groups (49.3+/−12.2 vs. 52.4+/−8.1%, 65.2+/−13.1 vs. 69.1+/−16.6ml/m 2 ). EPC spontaneously released after AMI and number of released EPC is correlated to the amount of neovascularization in the infarct zone. The number of EPC was not necessarily related to the functional improvement or attenuation of LV remodeling.

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