[Frontiers in Bioscience E2, 711-724, January 1, 2010]

Liver cell-mediated alleviation of acute ischemic myocardial injury

Shu Q. Liu, Yu H. Wu

Biomedical Engineering Department, Northwestern University, Evanston, IL 60208-3107, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Experimental procedures
3.1. Transgenic Mouse Model
3.2. Coronary Arterial Ligation
3.3. Preparation of liver cell extract
3.4. cDNA Microarray
3.5. Fluorescence Microscopy
3.6. TTC assay
3.7. TUNEL assay
3.8. Flow cytometry
3.9. Statistical Analysis
4. Results
4.1. Characterization of the Alb-Cre-EYFP mouse model
4.2. Mobilization of liver cells in response to myocardial ischemia
4.3. Disintegration of mobilized liver cells in the circulatory system
4.4. Alleviation of myocardial infarction in response to administration of liver cell extract
4.5. Gene upregulation in myocardial ischemia-conditioned liver cells
5. Discussion
5.1. Liver responses to myocardial ischemia
5.2. The fate of mobilized liver cells
5.3. Potential cardioprotective therapies based on liver cells
5.4. Potential cardioprotective factors from myocardial ischemia-conditioned liver cells
6. Acknowledgments
7. References

1. ABSTRACT

Cardiomyocyte injury occurs in myocardial ischemia, resulting in impairment of cardiac function. As the endogenous protective function of adult cardiomyocytes is limited, nonmyocytic cells may be activated to protect myocardium from ischemic injury. In this investigation, we demonstrated in a mouse model of myocardial ischemia that the liver was able to respond to myocardial ischemia to upregulate a number of genes encoding secreted proteins, mobilize its cells, and release cell contents into the circulatory system. These naturally occurring mechanisms suggested a possible cardioprotective role for myocardial ischemia-conditioned liver cells and inspired us to develop cardioprotective therapies based on these mechanisms. We demonstrated that administration of liver cell extract derived from myocardial ischemic mice, but not sham control mice, resulted in a significant reduction in acute myocardial infarction as well as the density of TUNEL+ cells in ischemic myocardium compared to administration of PBS at 2, 6, 12, and 24 hrs. These observations suggest that liver cells may respond to myocardial ischemia to express cardioprotective factors, which may be identified and used for alleviating myocardial infarction.