Heat shock proteins in cardiosurgery patients

Demidov, Oleg N.; Тыренко, В В; Свистов, А С; Komarova, Yelena Yuryevna; Karpishenko, Anatoly Ivanovich; Margulis, Boris A.; Shevchenko, Yu.L.

doi:10.1016/s1010-7940(99)00291-2

Cited by 42 publications

(33 citation statements)

References 22 publications

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“…[7][8][9] However, there are few reports on circulating HSPs in human diseases. [23][24][25] The early peak of inducible HSP70 in plasma after CABG as demonstrated in our study is striking.…”

Section: Discussionmentioning

confidence: 99%

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Inflammatory Response After Open Heart Surgery

et al. 2002

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Background-Coronary artery bypass grafting with the use of cardiopulmonary bypass is known to mediate an inflammatory response. The stress-inducible heat-shock protein (HSP) 70 has been detected in myocardial cells after CABG, and toll-like receptors (TLRs) are suggested as putative signaling receptors for the HSPs, mediating synthesis of inflammatory cytokines. The main aims of our study were to explore the release of HSP70 and the regulation of monocyte TLR-2 and TLR-4 expression after CABG. Methods and Results-Twenty patients referred for elective CABG were included in this study. Using immunoassays, we detected HSP70 in plasma after CABG, with peak concentration immediately after surgery. Interleukin-6 in plasma reached peak concentration 5 hours after surgery. Monocyte CD14, TLR-2, and TLR-4 expression, as analyzed by flow cytometry, was initially downregulated. On day 1, CD14 expression normalized, whereas TLR-2 and TLR-4 expression was upregulated. TLR-4 was significantly upregulated even on postoperative day 2. Additional experiments revealed that peritoneal macrophages from control (C3H/HeN) mice responded to HSP70 with release of tumor necrosis factor, whereas macrophages from mutated TLR-4 (C3H/HeJ) mice were unresponsive. In vitro, human adherent monocytes responded to recombinant HSP70 with interleukin-6 and tumor necrosis factor release. CD14 and TLR-4 monoclonal antibodies inhibited the cytokine response. Conclusions-In this study, we observed an immediate release of HSP70 into the circulation and a modulation of monocyte TLR-2 and TLR-4 expression after CABG. TLR-4 and CD14 appear to be involved in an HSP70-mediated activation of innate immunity. (Circulation. 2002;105:685-690.)

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Section: Discussionmentioning

confidence: 99%

“…7 Myocardial ischemia induces HSP70 as a stress response, 7 and HSP70 is increased in atrial tissue of patients with unstable angina. 8 Demidov and coworkers 9 found induction of HSP70 in myocardial cells in 40% of 33 patients undergoing CABG. Circulating inducible HSP70 after CABG has, to our knowledge, not been demonstrated previously.…”

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Inflammatory Response After Open Heart Surgery

et al. 2002

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“…However, HSPs function not only within the cell to chaperone proteins and protect tissues from stress and injury but also extracellularly to signal cell stress or trauma (4). HSP70 is released into the circulation after coronary artery bypass grafting (11) and acute myocardial infarction (9), and extracellular HSP70 has been shown to induce cytokine production in cultured mononuclear cells (2).Although several studies (8,17,29,35) have examined the expression of HSC70 in the myocardium during ischemiareperfusion, it is unknown whether the myocardium releases HSC70 during ischemia-reperfusion. Nor is it known whether extracellular HSC70 has any effect on the cellular or tissue…”

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confidence: 99%

“…Although several studies (8,17,29,35) have examined the expression of HSC70 in the myocardium during ischemiareperfusion, it is unknown whether the myocardium releases HSC70 during ischemia-reperfusion. Nor is it known whether extracellular HSC70 has any effect on the cellular or tissue inflammatory response.…”

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Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion

Zou¹,

Ao²,

Cleveland³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion. Am J Physiol Heart Circ Physiol 294: H2805-H2813, 2008. First published April 25, 2008 doi:10.1152/ajpheart.00299.2008.-Previous studies showed that Toll-like receptor 4 (TLR4) modulates the myocardial inflammatory response to ischemia-reperfusion injury, and we recently found that cytokines link TLR4 to postischemic cardiac dysfunction. Although TLR4 can be activated in cultured cells by endogenous agents including heat shock protein 70, how it is activated during myocardial ischemia-reperfusion is unknown. In the present study, we examined 1) whether heat shock cognate protein 70 (HSC70), which is constitutively expressed in the myocardium, is released during ischemia-reperfusion; 2) whether extracellular HSC70 induces the myocardial inflammatory response and modulates cardiac function; and 3) whether HSC70 exerts these effects via TLR4. We subjected isolated mouse hearts to global ischemia-reperfusion via the Langendorff technique. Immunoblotting and immunostaining detected the release of HSC70 from the myocardium during reperfusion. Treatment with an antibody specific to HSC70 suppressed myocardial cytokine expression and improved cardiac functional recovery after ischemia-reperfusion. Recombinant HSC70 induced NF-B activation and cytokine expression and depressed myocardial contractility in a TLR4-dependent manner. These effects required the substratebinding domain of HSC70. Fluorescence resonance energy transfer analysis of isolated macrophages demonstrated that extracellular HSC70 interacts with TLR4. Therefore, this study demonstrates for the first time that 1) the myocardium releases HSC70 during ischemiareperfusion, 2) extracellular HSC70 contributes to the postischemic myocardial inflammatory response and to cardiac dysfunction, 3) HSC70 exerts these effects through a TLR4-dependent mechanism, and 4) the substrate-binding domain of HSC70 is required to induce these effects. Thus extracellular HSC70 plays a critical role in regulating the myocardial innate immune response and cardiac function after ischemia-reperfusion.Toll-like receptor 4; cytokines; nuclear factor-B; messenger ribonucleic acid CARDIAC SURGERY OFTEN INVOLVES obligatory global myocardial ischemia-reperfusion, which causes a myocardial inflammatory response characterized by cytokine production (16, 18). Several proinflammatory cytokines, including TNF-␣, IL-1␤, and IL-6, contribute to myocardial injury after ischemia-reperfusion (12, 31). Preserving cardiac function after global ischemia-reperfusion therefore requires regulation of the myocardial inflammatory response. However, the signaling mechanisms underlying the myocardial inflammatory response to global ischemia-reperfusion are unclear.Previous studies implicated Toll-like receptor 4 (TLR4) signaling in the inflammatory response associated with myocardial ischemia-reperfusion injury. In mice treated with the TLR4 antagonis...

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“…The 70-kDa family of HSP (HSP70), in particular, plays a vital role in cellular protection and has been detected in various tissues subject to stress. 7,8 HSP70 expression was demonstrated in cardiovascular surgery patients, 9,10 and current experimental studies have demonstrated the efficacy of HSP70 induction before stress in reducing myocardial damage after ischemia-reperfusion. 11,12 However, this novel approach through the self-protective system has not yet been applied to CPB-induced inflammatory response.…”

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Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass–Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity

et al. 2002

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Background-Heat-shock protein 70 (HSP70) plays a major role in the pathophysiology of inflammation, and the induction of HSP70 before the onset of inflammation can reduce organ damage through a self-protective system. Glutamine is known to be an inducer of HSP70, and its preoperative administration seems useful in attenuating cardiopulmonary bypass (CPB)-induced inflammatory response. Methods and Results-Adult male Sprague-Dawley rats (group G, received 100 mg/kg of glutamine via the right jugular vein 3 times per day for 1 week and just before the initiation of CPB; group C served as control) underwent CPB (60 minutes, 100 mL/kg per minute, 34°C) and were killed 3 hours after the termination of CPB. Group G showed significantly lower plasma concentrations of interleukin-6 and interleukin-8 after CPB termination. Myocardial and respiratory damages were significantly attenuated in group G, as evidenced by Langendorff perfusion, respiratory index, and neutrophil adherence. HSP70 expressions in the heart, lung, and liver were detected only in group G before CPB and were markedly stronger in group G 3 hours after CPB termination. Although plasma nitrateϩnitrite concentrations were not significantly different between the groups, endothelial-constitutive nitric oxide synthase (NOS) activity was markedly preserved and inducible NOS activity was markedly attenuated in the tissues of group G. Conclusions-These results suggest that preoperative glutamine administration induces HSP70 expression before CPB and attenuates CPB-induced inflammation by regulating NOS activity, which may be a prospective management for conferring tolerance to CPB-induced inflammatory response through a self-protective mechanism. (Circulation. 2002; 106:2601-2607.)

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Heat shock proteins in cardiosurgery patients

Abstract: HSP72 is implicated in cardioprotection in combination with some other factors, and its pre-operational level, among other parameters, might be of prognostic value.

Cited by 42 publications

References 22 publications

Inflammatory Response After Open Heart Surgery

Inflammatory Response After Open Heart Surgery

Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion

Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass–Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity

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