17β-Estradiol enhances the recruitment of bone marrow-derived endothelial progenitor cells into infarcted myocardium by inducing CXCR4 expression.

Abstract

BACKGROUND:

17β-Estradiol (E2) has been thought to produce cardioprotective effects by mediating bone marrow-derived endothelial progenitor cells (EPC) for cardiac repair in the setting of acute myocardial infarction (AMI). However, the underlying mechanism of action of E2 on EPC remains unclear. CXCR4 is a critical modulator in homing of EPC. Accordingly, we hypothesized that E2 exerts beneficial effects through enhancing EPC homing to infarcted myocardium via mediating CXCR4 pathway.

METHODS AND RESULTS:

Migratory capacity and CXCR4 expression of EPC from ovariectomized BALB/C mice were detected after being incubated with various E2 concentrations for various incubation times. For in vivo studies, EPC were labeled with superparamagnetic ion oxide (SPIO) for tracing, and ovariectomized mice were grouped (n=11) after inducing AMI to receive saline without cells or with 3 × 10(6) non-preconditioned EPC, 100 nmol/L E2 preconditioned EPC, CXCR4 inhibitor AMD3100 (5 μg/mL) preconditioned EPC, or EPC pretreated with E2 plus AMD3100. The number of homing EPC in infarcted myocardium and left ventricular (LV) function, dimensions and fibrosis were measured. In vitro data showed that E2 increased migratory activity and functional CXCR4 expression of EPC. However, these effects were completely blocked by AMD3100. In vivo data in E2 group displayed a greater number of homing EPC, decreased fibrosis of LV, and significant improvement in cardiac function. Nevertheless, effects of E2 preconditioning were abrogated by AMD3100.

CONCLUSIONS:

We conclude that E2 enhances the recruitment of EPC into infarcted myocardium by up-regulating functional CXCR4 expression, resulting in improving recovery after myocardial infarction.

• Authors: Haiqing Li, Jun Liu, Xiaofeng Ye, Xi Zhang, Zhe Wang, Anqing Chen, Mi Zhou, Qiang Zhao
• Journal: International journal of cardiology (Int J Cardiol) Vol. 162 Issue 2 Pg. 100-6 (Jan 10 2013) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 21636145 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Chemokine CXCL12
• Cxcl12 protein, mouse
• DNA Primers
• Estrogens
• Receptors, CXCR4
• Estradiol

Topics

• Animals
• Bone Marrow Cells (drug effects)
• Cell Movement (drug effects)
• Cells, Cultured
• Chemokine CXCL12 (genetics, metabolism)
• DNA Primers (chemistry)
• Endothelial Cells (drug effects)
• Estradiol (pharmacology, therapeutic use)
• Estrogens (pharmacology, therapeutic use)
• Female
• Gene Expression Regulation
• Mice
• Mice, Inbred BALB C
• Myocardial Infarction (drug therapy, metabolism, physiopathology)
• Receptors, CXCR4 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Stem Cells (drug effects)
• Ventricular Function, Left (drug effects)