Heat shock protein 27 is increased in cyanotic tetralogy of Fallot myocardium and is associated with improved cardiac output and contraction
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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 non-cyanotic 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 pre-operative status) and (2) after 15 min during ischemia until surgery was complete. The cyanotic group had significantly increased haematocrit, lower O2 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 (p = 0.03). In the cyanotic group, baseline HSP 27 expression also significantly correlated with oxygen extraction ratio (p = 0.028), post-operative basal septal velocity (p = 0.036) and mixed venous oxygen saturation (p = 0.02), markers of improved cardiac output/contraction. Increased HSP 27 expression and associated improved right ventricle function and systemic perfusion supports a cardio-protective effect of HSP 27 in cyanotic TOF.
KeywordsTetralogy of Fallot Heat shock protein 27 Right ventricle Myocardium Cyanotic Non-cyanotic
This work was supported by Yorkhill Children's Foundation.
- Aloy MT, Hadchity E, Bionda C, Diaz-Latoud C, Claude L, Rousson R, Arrigo AP, Rodriguez-Lafrasse CC (2008) Protective role of Hsp27 protein against gamma radiation-induced apoptosis and radiosensitization effects of Hsp27 gene silencing in different human tumor cells. Int J Radiat Oncol Biol Phys 70:543–553PubMedCrossRefGoogle Scholar
- Hollander JM, Martin JL, Belke DD, Scott BT, Swanson E, Krishnamoorthy V, Dillmann WH (2004) Overexpression of wild–type heat shock protein 27 and a nonphosphorylatable heat shock protein 27 mutant protects against ischemia/reperfusion injury in a transgenic mouse model. Circ 110:3544–3552CrossRefGoogle Scholar
- Jayakumar J, Suzuki K, Khan M, Smolenski RT, Farrell A, Latif N, Raisky O, Abunasra H, Sammut IA, Murtuza B, Amrani M, Yacoub MH (2000) Gene therapy for myocardial protection: transfection of donor hearts with heat shock protein 70 gene protects cardiac function against ischemia reperfusion injury. Circ 102:III302–III306CrossRefGoogle Scholar
- VanderHeide RS (2002) Increased expression of HSP27 protects canine myocytes from simulated ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 282:H935–H941Google Scholar
- Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castañeda AR, Newburger JW, Wessel DL (1995) Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circ 92:2226–2235CrossRefGoogle Scholar