Heat shock protein 27 protects the heart against myocardial infarction

Efthymiou, Christopher Andrew; Mocanu, Mihaela M.; Belleroche, Jackie de; Wells, Dominic J.; Latchmann, David S.; Yellon, Derek M.

doi:10.1007/s00395-004-0483-6

Cited by 109 publications

(75 citation statements)

References 14 publications

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“…Most of the current knowledge has come from animal models or limited studies on adult cardiac disease. HSP 27 expression has been shown to protect against myocardial infarction (Willis and Patterson 2010;Efthymiou et al 2004) and is increased in the rat left ventricle myocardium after coronary ligation and in human patients with dilated cardiomyopathy (Knowlton et al 1998). Studies on HSP 27 knockout mice have shown that, at least in this species, HSP 27 is not essential for cardiac development but plays a role in the antioxidative response during ischemia-reperfusion injury (Willis and Patterson 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Although studied in other fields of medicine, the role of HSPs before, and following paediatric cardiac surgery, is not understood. However, it is becoming clear from adult human and animal studies that HSPs may have an important role in protecting the damaged heart, which accumulates misfolded proteins (Schmitt et al 2002;Taggart et al 1997;Jayakumar et al 2000;Hollander et al 2004;Yet et al 2001;Aloy et al 2008;Franklin et al 2005;Efthymiou et al 2004 andKnowlton et al 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Only a few of the smaller HSPs, including HSP 27, are increased in cells subjected to stress (Efthymiou et al 2004). HSP 27 is involved in protein folding and in the apoptotic/ programmed cell death pathway.…”

Section: Introductionmentioning

confidence: 99%

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Heat shock protein 27 is increased in cyanotic tetralogy of Fallot myocardium and is associated with improved cardiac output and contraction

Walker¹,

Danton

Peng

et al. 2013

Cell Stress and Chaperones

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Tetralogy of Fallot (TOF) is a congenital heart condition in which the right ventricle is exposed to cyanosis and pressure overload. Patients have an increased risk of right ventricle dysfunction following corrective surgery. Whether the cyanotic myocardium is less tolerant of injury compared to non-cyanotic is unclear. Heat shock proteins (HSPs) protect against cellular stresses. The aim of this study was to examine HSP 27 expression in the right ventricle resected from TOF patients and determine its relationship with right ventricle function and clinical outcome. Ten cyanotic and ten noncyanotic patients were studied. Western blotting was used to quantify HSP 27 in resected myocardium at (1) baseline (first 15 min of aortic cross clamp and closest representation of preoperative status) and (2) after 15 min during ischemia until surgery was complete. The cyanotic group had significantly increased haematocrit, lower O 2 saturation, thicker interventricular septal wall thickness and released more troponin-I on post-operative day 1 (p<0.05). HSP 27 expression was significantly increased in the <15 min cyanotic compared to the <15 min non-cyanotic group (p00.03). In the cyanotic group, baseline HSP 27 expression also significantly correlated with oxygen extraction ratio (p00.028), post-operative basal septal velocity (p00.036) and mixed venous oxygen saturation (p00.02), markers of improved cardiac output/contraction. Increased HSP 27 expression and associated improved right ventricle function and systemic perfusion supports a cardioprotective effect of HSP 27 in cyanotic TOF.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heat shock protein 27 is increased in cyanotic tetralogy of Fallot myocardium and is associated with improved cardiac output and contraction

Walker¹,

Danton

Peng

et al. 2013

Cell Stress and Chaperones

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“…Reduced Hsp70 expression level induces more infarction volume of focal cerebral ischemia in knockout mice of hsp70.1 (gene encoding inducible Hsp70) (Lee et al, 2001(Lee et al, , 2004. Overexpression of Hsp27 and aB-crystallin (HspB5) in transgenic mice showed a reduced amount of infarction (Ray et al, 2001;Efthymiou et al, 2004) and attenuated cardiomyocyte apoptosis (Ray et al, 2001). In the heart of double knockout mice of aB-crystallin and HspB2, which have shared regulatory elements in the promoter region, ischemia-reperfusion exhibits contractile dysfunction and increased myocardial infarction ( Figure 1 Proposed pathway in amyloid assembly and actions of molecular chaperones.…”

Section: Molecular Chaperones As Regulators Of Cell Death a Hishiya Amentioning

confidence: 99%

Molecular chaperones as regulators of cell death

Hishiya

Takayama

2008

Oncogene

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“…A second important cardioprotective element, common to PreC and PostC, is represented by chaperone proteins, also known as HSPs [12,18,41,63]. We have previously identified melusin as a new musclespecific chaperone protein binding to the cytoplasmic domain of β1 integrin and acting as mechanical stretch sensor of the cytoskeleton [8].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the muscle-specific protein, melusin, protects from cardiac ischemia/reperfusion injury

et al. 2014

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Melusin is a muscle-specific protein which interacts with β1 integrin cytoplasmic domain and acts as chaperone protein. Its overexpression induces improved resistance to cardiac overload delaying left ventricle dilation and reducing the occurrence of heart failure. Here we investigated possible protective effect of melusin overexpression against acute ischemia/reperfusion (I/R) injury with or without Postconditioning cardioprotective maneuvers.Melusin-transgenic (Mel-TG) mice hearts were subjected to 30 minutes global ischemia followed by 60 minutes reperfusion. Interestingly, infarct size (IS) was reduced in Mel-TG mice hearts compared to wildtype (WT) hearts (40.3±3.5% Mel-TG vs. 59.5±3.8% WT hearts; n= 11 animals/group; P<0.05). The melusin protective effect was also demonstrated by measuring LDH release, which was 50% lower in Mel-TG compared to WT. Mel-TG hearts had a higher baseline level of AKT, ERK1/2 and GSK3β phosphorylation, and displayed increased phospho-kinases level after I/R compared to WT mice. Postischemic Mel-TG hearts displayed also increased levels of the antiapoptotic factor phospho-BAD.Importantly pharmacological inhibition of PI3K/AKT (Wortmannin) and ERK1/2 (U0126) pathways abrogated the melusin protective effect. Notably, HSP90, a chaperone known to protect heart from I/R injury, showed high levels of expression in the heart of Mel-TG mice suggesting a possible collaboration of this molecule with AKT/ERK/GSK3β pathways in the melusin-induced protection. Postconditioning, known to activate AKT/ERK/GSK3β pathways, significantly reduced IS and LDH release in WT hearts, but had no additive protective effects in Mel-TG hearts. These findings implicate melusin as an enhancer of AKT and ERK pathways and as a novel player in cardioprotection from I/R injury.

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Heat shock protein 27 protects the heart against myocardial infarction

Cited by 109 publications

References 14 publications

Heat shock protein 27 is increased in cyanotic tetralogy of Fallot myocardium and is associated with improved cardiac output and contraction

Heat shock protein 27 is increased in cyanotic tetralogy of Fallot myocardium and is associated with improved cardiac output and contraction

Molecular chaperones as regulators of cell death

Overexpression of the muscle-specific protein, melusin, protects from cardiac ischemia/reperfusion injury

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