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

2017 ◽  
Vol 54 (6) ◽  
pp. 321-328 ◽  
Author(s):  
Gabi Demetz ◽  
Robert A.J. Oostendorp ◽  
A. Melanie Boxberg ◽  
Wibke Sitz ◽  
Eliane Farrell ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Left Ventricular Function ◽  
Progenitor Cells ◽  
Ventricular Function ◽  
Endothelial Progenitor Cells ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Insulin Like Growth Factor ◽  
Endothelial Progenitor

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.

Temporal dissociation of left ventricular function and remodeling following experimental myocardial infarction in rats

1999 ◽  
Vol 5 (3) ◽  
pp. 213-223 ◽  
Author(s):  
Scott D. Solomon ◽  
Sally C. Greaves ◽  
Mamdouh Rayan ◽  
Peter Finn ◽  
Marc A. Pfeffer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction

Endothelial‐like cells expanded from CD34 + blood cells improve left ventricular function after experimental myocardial infarction

2005 ◽  
Vol 19 (8) ◽  
pp. 992-994 ◽  
Author(s):  
Ilka Ott ◽  
Ulrich Keller ◽  
Martina Knoedler ◽  
Katharina S. Götze ◽  
Katharina Doss ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Blood Cells ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction

Abstract 3952: Late Outgrowth Endothelial Progenitor Cells From Patients With AMI Improve Left Ventricular Ejection Fraction In Experimental Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Martina Knoedler ◽  
Eliane Weidl ◽  
Sandra Gawehn ◽  
Maren Schurmann ◽  
Andreas Stein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Myocardial Function ◽  
Experimental Myocardial Infarction ◽  
Therapeutic Use ◽  
Endothelial Progenitor ◽  
Cd34 Cells

Background: Recent studies suggest that endothelial progenitor cells (EPC) from bone marrow or peripheral blood improve myocardial function in experimental myocardial infarction (MI). Since applications for cell therapy are limited by the number of available cells, expansion of EPC may facilitate its therapeutic use in ischemic disease. The aim of this study was to expand late outgrowth EPC from peripheral blood from patients with acute myocardial infarction, characterize them and investigate their therapeutic effect in experimental MI. Methods and Results: Venous blood samples were obtained from patients with acute MI (n=51), stable angina (sAP, n=57) and healthy controls (H,n=47). CD34+ cells were isolated using immunomagnetic beads (Miltenyi Biotec). CD34+ cells cultured on fibronectin in endothelial cell medium formed colonies after 1–2 weeks and were further expanded for up to 3 months to generate late outgrowth EPC (eEPC). Expansion was observed up to 2.9x10′9 (MI), 11x10′9 (sAP) and 7x10′9 cells (H) with a mean culture duration of 61 days. Expanded cells showed an endothelial morphology and expressed endothelial surface markers (CD31, VEGF-R2, CD105). Intramyocardial transplantion of 1x10′6 eEPC in experimental myocardial infarction in athymic nude rats revealed improvement in echocardiographic ejection fraction after 2 weeks. This was associated with enhanced vessel density after 1 week and increased mRNA expression of HGF. No differences in infarct size were observed. Similarly in a chronic model of myocardial infarction (eEPC transplantation 1 week after MI) myocardial function significantly improved after 5 weeks in comparison to the control group. Conclusion: Expansion of eEPC from circulating CD34+ cells in patients with coronary artery disease is feasible and improves myocardial function after local transplantation in acute and chronic myocardial infarction. The large number of generated eEPC may prove benefical for therapeutic use and this advantage may prevail time-consuming expansion procedures.

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