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Activated cell survival cascade protects cardiomyocytes from cell death in Tako‐Tsubo cardiomyopathy
Author(s) -
Nef Holger M.,
Möllmann Helge,
Hilpert Pirmin,
Troidl Christian,
Voss Sandra,
Rolf Andreas,
Behrens Christopher B.,
Weber Michael,
Hamm Christian W.,
Elsässer Albrecht
Publication year - 2009
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfp076
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , pten , medicine , phosphorylation , heart failure , programmed cell death , phosphatase , cardiomyopathy , apoptosis , microbiology and biotechnology , cancer research , signal transduction , biology , biochemistry
Aims Tako‐Tsubo cardiomyopathy (TTC) is characterized by rapid regeneration of contractile dysfunction. From recent studies it is known that excessive catecholamine levels due to emotional or physical stress might play a central role. After sympathetic activation, the PIK3/AKT pathway is a key regulator of many cellular responses, including cytoprotective effects. Thus, the purpose of this study was to investigate whether the PIK3/AKT pathway plays a pivotal role in TTC. Methods and results A total of 16 consecutive patients diagnosed with TTC were studied. Left ventricular biopsies were taken during the acute phase and after functional recovery. Specimens were examined by quantitative RT–PCR and western blotting. Representative genes of the PI3K/AKT pathway (PIK3‐R1, PTEN, GSK3β, mTOR, PP2A, eIF4E) were compared with left ventricular controls from non‐transplanted healthy hearts. PI3K expression was increased during the acute phase and after functional recovery. AKT protein levels were unaltered, but phosphorylation significantly increased during the acute phase. Both PTEN (PI3K antagonist) and PP2 (unspecific phosphatase) were down‐regulated. Phosphorylation of the PI3K/AKT downstream target mTOR was increased, while expression of both GSK3 isoforms was decreased. The Bax/Bcl2 ratio was increased in the acute and recovery phases. Conclusion PI3K/AKT signalling is activated in TTC. This activated cell survival cascade might protect cardiomyocytes from cell death and also contribute to rapid regeneration in TTC.