Abstract:
AIMS: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 beta-adrenoceptor stimulation is associated with alteration in gene expression of Ca(2+)-regulatory proteins. Thus, the present study investigated the gene expression of crucial proteins [sarcoplasmic Ca(2+) ATPase (SERCA2a), sarcolipin (SLN), phospholamban (PLN), ryanodine receptor (RyR2), and sodium-calcium exchanger (NCX)] involved in the Ca(2+)-regulating system in TTC. METHODS AND RESULTS: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 Ca(2+)-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-Ser(16) and PLN-Thr(17). No changes could be documented for NCX and RyR2. CONCLUSION:In TTC, ventricular expression of SLN and dephosphorylation of PLN potentially result in a reduced SERCA2a activity and its Ca(2+) affinity. Thus, the TTC is associated with specific alteration of Ca(2+)-handling proteins, which might be crucial for contractile dysfunction.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Nef HM,Möllmann H,Troidl C,Kostin S,Voss S,Hilpert P,Behrens CB,Rolf A,Rixe J,Weber M,Hamm CW,Elsässer Adoi
10.1093/eurheartj/ehp240subject
Has Abstractpub_date
2009-09-01 00:00:00pages
2155-64issue
17eissn
0195-668Xissn
1522-9645pii
ehp240journal_volume
30pub_type
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pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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