Activated cell survival cascade protects cardiomyocytes from cell death in Tako‐Tsubo cardiomyopathy

Abstract

AimsTako-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 resultsA 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, GSK3b, 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. ConclusionPI3K/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.--

Amlodipine has a preventive effect on temporal left ventricular hypokinesia after emotional stress compared with an angiotensin II receptor blocker

“…Just after induction of general anesthesia, the heart rate in the three groups was significantly reduced, but there was no significant difference in heart rate between the three groups after IMO. The data are expressed as mean value ± SD, *p \ 0.05 between amlodipine versus vehicle at completion of IMO J Med Ultrasonics (2013) 40: 3-7 5 enhancing protein biosynthesis, which is essential for myocardial regeneration and improvement of left ventricular function [17]. In a normal rat, FAC is about 80 % after anesthesia, so FAC of 60 % means hypokinesia in rats.…”

The Sympathetic Nervous System in the Pathogenesis of Takotsubo Syndrome

“…41 This switch to G i signaling may be protective in the acute phase of TS by activating several pathways that reduce catecholamine toxicity and decrease apoptosis. 82,83 …”

Takotsubo Cardiomyopathy

“…A rapidly accumulating body of evidence has led to very interesting insights into the possible pathophysiology of TTC. Most current hypotheses are based on cathecholamine surges in the setting of acute emotional or physical stress leading to catecholamine-related cardiac toxic effects (32,(44)(45)(46)(47)(48)(49) and was first suggested by Wittstein and colleagues (16). In this section we examine various advancements in understanding TTC pathophysiology.…”