Emotional Stress-Induced Tako-tsubo Cardiomyopathy: Animal Model and Molecular Mechanism


Address for correspondence: Takashi Ueyama, M.D., Ph.D., Department of Anatomy and Cell Biology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City 641-8509, Japan. Voice: +81 73 441 0616; fax: +81 73 441 0616. e-mail: tueyama@wakayama-med.ac.jp


Abstract: Emotional or physical stress triggers Tako-tsubo cardiomyopathy in postmenopausal females, which is characterized by an elevation of the ST segment in the electrocardiogram (ECG) and left ventricular apical ballooning in the left ventriculogram (LVG). Immobilization stress (IMO) of rats can reproduce these ECG and LVG changes, both of which are normalized by combined blockade of α- and β-adrenoceptors. An increase of serum estrogen partially attenuated these cardiac changes. IMO induced a rapid activation of p44/p42 mitogen-activated protein kinase, followed by a transient upregulation of immediate early genes (IEG) in the coronary artery and myocardium. Blocking of both α- and β-adrenoceptors eliminated the upregulation of IEG induced by stress, while α- or β-agonists upregulated IEG in the perfused heart. Heat shock protein 70 was induced in the aorta, coronary artery, and the myocardium. Natriuretic peptide genes (ANP and BNP) were also upregulated in the myocardium. Sequential gene expression can be considered as an adaptive response to stress. Activation of α- or β-adrenoceptors is the primary trigger of emotional stress-induced cardiac changes.