Abnormalities in intracellular Ca2+ regulation contribute to the pathomechanism of Tako-Tsubo cardiomyopathy
Open Access
- 13 June 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in European Heart Journal
- Vol. 30 (17), 2155-2164
- https://doi.org/10.1093/eurheartj/ehp240
Abstract
The Tako-Tsubo cardiomyopathy (TTC) is characterized by a transient contractile dysfunction that has been assigned to excessive catecholamine levels after episodes of severe emotional or physical stress. Several studies have indicated that β-adrenoceptor stimulation is associated with alteration in gene expression of Ca2+-regulatory proteins. Thus, the present study investigated the gene expression of crucial proteins [sarcoplasmic Ca2+ ATPase (SERCA2a), sarcolipin (SLN), phospholamban (PLN), ryanodine receptor (RyR2), and sodium-calcium exchanger (NCX)] involved in the Ca2+-regulating system in TTC. In 10 consecutive patients, TTC was diagnosed by coronary angiography, ventriculography, and echocardiography. Endomyocardial biopsies were taken during the phase of severely impaired left ventricular (LV) function and after functional recovery. Non-diseased LV tissue from three donor hearts not used for transplantation served as healthy controls. Expression levels of Ca2+-regulatory proteins were analysed by means of real-time PCR, western blot, and immunohistochemistry. SLN, predominantly expressed in the atrial component, showed a remarkable ventricular expression in TTC patients. Gene expression of SERCA2a was significantly down-regulated. Conversely, PLN/SERCA2a ratio was increased. For PLN, dephosphorylation was documented using western blot and immunostaining of PLN-Ser16 and PLN-Thr17. No changes could be documented for NCX and RyR2. In TTC, ventricular expression of SLN and dephosphorylation of PLN potentially result in a reduced SERCA2a activity and its Ca2+ affinity. Thus, the TTC is associated with specific alteration of Ca2+-handling proteins, which might be crucial for contractile dysfunction.Keywords
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