Received November 28, 2007
Revised February 11, 2008
Accepted after revision February 22, 2008
Heart/Cardiac Muscle [240]
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Myocardial Ischemia/Reperfusion Injury in Hematopoietic Cell-Restricted 
1 Integrin Knockout Mice
Bernhard Metzler 1*,
Bernhard Haubner 1,
Elisabetta Conci 1,
Jakob Voelkl 1,
Johannes Jehle 1,
Martina Bauer 2,
Dominik Wolf 3,
Otmar Pachinger 1,
Qingbo Xu 4
1 Medical University Innsbruck
2 Max Planck Institute of Biochemistry, martinsried
3 Tyrolean Cancer Research Institute
4 Kings College London
* To whom correspondence should be addressed. E-mail: bernhard.metzler{at}uki.at.
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Abstract |
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Objective: Evidence indicates that the intercellular adhesion molecule-1 and its counter-receptor 
2 integrin are cardioprotective proteins during myocardial ischemia/reperfusion, but no data are available concerning the role of blood cell 1 integrins in this process. We studied the effects of temporary myocardial ischemia and reperfusion in blood cell-restricted 1 integrin knockout mice (1-/-).
Methods: The left descending coronary artery in conditional 1-/- integrin (1-/-), 1integrin +/+ (1+/+), and 1 integrin -/- bone marrow chimeric (1-/- BM) mice was ligated for 30 min followed by reperfusion of either 3 h or 3 weeks. Plasma levels of troponin T were evaluated as an index of cardiac cellular damage. The histological evaluation of tissue damage was performed with hematoxilin and eosin stained sections. Cell infiltrations in the ischemic area were investigated by immunofluorescence studies.
Results: Plasma troponin T was at a similar level in 1-/-, 1+/+, and 1 -/- BM mice treated with 30 min ischemia and 3 h reperfusion. Histological analysis showed that ischemia/reperfusion resulted in marked myocardial injury in all groups of animals, but the damage score of the hearts was not significantly different between 1-/-, 1+/+, and 1 -/- BM mice after 3 h of reperfusion following 30 min of ischemia (2.8±0.5 vs. 2.6±0.5 vs. 2.8±0.6, NS). Furthermore, no difference in scar sizes in ischemia-injured hearts was found 3 weeks after ischemia. Semi-quantification of cells demonstrated that compared to 1 +/+ mice, the number of infiltrating neutrophils was significantly reduced in 1-/- and 1-/- BM mice, whereas MAC-1-positive cells in the ischemic regions were similar in myocardial tissues of all groups.
Conclusion: Absence of 1 integrin expression in hematopoietic cells results in reduced neutrophil infiltration in the ischemic regions, but does not influence myocardial damage of ischemic hearts.
Key Words:
Heart, Ischaemia, Myocardium
