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.