Unstable angina activates myocardial heat shock protein 72, endothelial nitric oxide synthase, and transcription factors NFκB and AP-1

Valen, Guro; Hansson, Göran K.; Dumitrescu, A; Vaage, Jarle

doi:10.1016/s0008-6363(00)00071-7

Cited by 75 publications

(43 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pathological and autopsy studies have reported that rupture or erosion of multiple vulnerable plaques and subsequent formation of thrombus are the most important mechanisms leading to ACS, whereas SA closely correlates with the stability of an atherosclerotic plaque (Hong et al 2004). Consistent with our results, increased Hsp70 levels have been detected in heart biopsies from patients with unstable, as compared with stable angina (Valen et al 2000). It is possible that soluble Hsp70 release into the circulation is higher in the sudden fissure or rupture of unstable plaque, and acute events, following AMI for example, rather than in stable plaque.…”

Section: Discussionsupporting

confidence: 91%

Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome

Zhang

Zhou

et al. 2010

Cell Stress and Chaperones

View full text Add to dashboard Cite

Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti-Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend<0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend= 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P<0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk.

show abstract

Section: Discussionsupporting

confidence: 91%

Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome

Zhang

Zhou

et al. 2010

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…19 Unstable angina activates cardiac heat shock protein 72, eNOS, and the transcription factor NFkB in patients with recent symptoms. 20 We speculate that, from an adaptive point of view, it appears sensible for an organism subjected to an acute ischemic event or inflammation of another etiology to defend itself against a possible next event in the same or another organ through increasing endogenous protection. The present findings pinpoint that organ protection is generated by ischemia, rather than by ischemia and reperfusion, and may thus represent a key to the pathway of solving the preconditioning enigma.…”

Section: Discussionmentioning

confidence: 92%

Spontaneous Ischemic Events in the Brain and Heart Adapt the Hearts of Severely Atherosclerotic Mice to Ischemia

Tokuno

Hinokiyama

Tokuno

et al. 2002

ATVB

View full text Add to dashboard Cite

Abstract-To investigate if spontaneous ischemic events in mice with severe multi-organ atherosclerosis could adapt to ischemia, apolipoprotein E/LDL receptor knockout mice were fed an atherogenic diet for 7 to 9 months. Signs of spontaneous ischemia occurred. One to two days later, hearts were excised, Langendorff-perfused with induced global ischemia, and compared with mice without signs of disease. In vivo heart or brain infarctions were verified by heart histology and/or increased serum levels of cardiac troponin T and S100B. Hearts of mice with spontaneous ischemic events had improved function and reduced Langendorff-induced infarctions. To investigate the remote preconditioning effect of brain ischemia, bilateral ligation of the internal carotid arteries was performed in C57BL6 mice. Twenty-four hours later, their isolated hearts were protected against induced global ischemia. A possible role of inducible NO synthase (iNOS) was studied in iNOS knock out mice, who were not preconditioned by induced brain ischemia. Cardiac iNOS was unchanged 24 hours after preconditioning, suggesting that NO is a trigger rather than a mediator of protection. These findings suggest that spontaneous ischemic events in the brain and heart adapt the heart to ischemia. This can be mimicked by induced brain ischemia, with iNOS as a key factor of protection. Key Words: ischemic preconditioning Ⅲ remote preconditioning Ⅲ atherosclerosis Ⅲ brain ischemia Ⅲ inducible nitric oxide synthase C ardiac adaptation to ischemia can be achieved experimentally by ischemic preconditioning, transient episodes of ischemia and reperfusion before sustained ischemia.

show abstract

“…[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%

“…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.…”

mentioning

confidence: 99%

Inflammatory Response After Open Heart Surgery

et al. 2002

View full text Add to dashboard Cite

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.)

show abstract

Unstable angina activates myocardial heat shock protein 72, endothelial nitric oxide synthase, and transcription factors NFκB and AP-1

Cited by 75 publications

References 29 publications

Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome

Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome

Spontaneous Ischemic Events in the Brain and Heart Adapt the Hearts of Severely Atherosclerotic Mice to Ischemia

Inflammatory Response After Open Heart Surgery

Contact Info

Product

Resources

About