Upregulation of heme oxygenase-1 in an animal model of Takotsubo cardiomyopathy.

BACKGROUND

Disturbance of the coronary microcirculation and catecholamine intoxication, which may be responsible for the pathogenesis of takotsubo cardiomyopathy, could trigger an oxidative stress response in the heart.

METHODS AND RESULTS

Expression and localization of inducible heme oxygenase-1 (HO-1), which is an oxidative stress-related factor in the heart of immobilization stressed (IMO) rats, an animal model of takotsubo cardiomyopathy, were investigated by real-time reverse transcriptase-polymerase chain reaction and in situ hybridization histochemistry and immunohistochemistry. In response to IMO, the levels of HO-1 mRNA in the heart and in the aorta were slightly increased at 90 min, and increased 3-fold at 3 h compared with control levels. The signals for HO-1 mRNA were expressed on scatted cells in the myocardium and aortic adventitia. Double fluorescence immunohistochemistry showed that HO-1 immunoreactive cells were also ED1 and ED2 positive, indicating that they were macrophages. The numbers of ED1 and ED2 positive cells were constant, whereas the number of HO-1 positive cells was increased 5-fold at 6 h compared with control levels. Blocking of alpha- and beta-adrenoceptors attenuated IMO-induced upregulation of HO-1 mRNA levels in the heart.

CONCLUSIONS

Emotional stress and a surge of catecholamine upregulate HO-1 in the cardiac and aortic macrophages.