Increased Level of Hsp27 but Not of Hsp72 in Human Heart Allografts in Relation to Acute Rejection1

Schimke, Ingolf; Lutsch, Gudrun; Schernes, Ulrike; Kruse, Ingrid; Dübel, Hans-Peter; Pregla, Reinhard; Hummel, Manfred; Meyer, Rudolf; Stahl, Joachim

doi:10.1097/00007890-200012270-00005

Cited by 15 publications

(12 citation statements)

References 10 publications

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“…Taken together, these results strongly suggest vascular expression of HSP27 is associated with freedom from CAV. It has been previously reported that HSP27 is diffusely expressed by cardiac myocytes of transplanted hearts, 13 but blood vessels were not investigated. Little is known about expression of HSP27 in normal and diseased human blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 27 Is Associated With Freedom From Graft Vasculopathy After Human Cardiac Transplantation

Souza

Wait

Mitchell

et al. 2005

Circulation Research

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Experimental studies have suggested that protective genes protect allografts from cardiac allograft vasculopathy (CAV), the major complication after cardiac transplantation. Here we have sought to confirm this hypothesis using long-term heart transplant recipients. Twenty-two patients that were 9 years or older after transplant were investigated; 11 of these were without angiographic evidence of CAV; 11 had developed early CAV at 1 to 3 years after transplant. To identify proteins that may act as protectors from CAV, a global proteomic approach was used comparing cardiac biopsies from 12 patients taken within the first 2 weeks after transplant and those taken after 9 years from the same patient. Proteins were separated by 2-D gel-electrophoresis, detected by silver staining, and analyzed using Progenesis software. A particular protein spot was found in 4/6 biopsies from patients without CAV, but absent from 5/6 biopsies from those with CAV (P=0.24); however, quantitative analysis of spot intensity showed a significant difference (0.061+/-0.05 versus 0.003+/-0.01, P=0.04). This spot was identified by mass spectrometry and a combination of techniques as a diphosphorylated form of HSP27. Immunohistochemistry of further biopsies not only validated that HSP27 was more abundantly expressed on biopsies without CAV but also showed it to be localized to blood vessels. In contrast, vessels from patients with CAV did not express HSP27 (P=0.028x10(-4)). Immunohistochemistry of 12 further early biopsies and nontransplanted heart showed HSP27 to be present in normal blood vessels. These findings suggest that expression of a specific diphosphorylated form of HSP27 is associated with healthy blood vessels; it appears to be lost from vessels of patients with graft vasculopathy.

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Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 27 Is Associated With Freedom From Graft Vasculopathy After Human Cardiac Transplantation

Souza

Wait

Mitchell

et al. 2005

Circulation Research

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“…Increased levels of Hsp27 were found in cardiac biopsy specimens associated with acute rejection after transplantation, but its cellular effects are uncertain. (13) Late after transplantation also, Hsp27 expression in vessels was found to correlate with freedom from cardiac allograft vasculopathy after cardiac transplantation. (11)…”

Section: Discussionmentioning

confidence: 99%

“…(10) The smaller heat shock proteins have been less investigated as source of alloimmunity, but Hsp27 expression has been correlated with allograft rejection after cardiac and renal transplantation. (11–13) However, the research as of now does not clearly indicate whether the increased expression of Hsps is a cytoprotective result of the cellular stress induced by transplantation or whether the increased expression is an antigenic stimulus eliciting allograft rejection.…”

mentioning

confidence: 99%

The role of heat shock protein 27 in bronchiolitis obliterans syndrome after lung transplantation

Wood

Nunley

Moffatt-Bruce

et al. 2010

The Journal of Heart and Lung Transplantation

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Background-Heat shock proteins (Hsps) are a family of evolutionary conserved proteins classified according to their size as small and large Hsps. They have a cytoprotective role and have been shown recently to be immunogenic molecules. In addition, self-reactivity to Hsps has been implicated in various autoimmune diseases and in the development of alloimmunity. The purpose of this study was to examine the relationship of large and small Hsps and anti-Hsp antibodies in recipients of lung transplantation (LTX) who have bronchiolitis obliterans syndrome (BOS).

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“…Heat shock protein-27 is constitutively expressed in human cardiomyocytes ( 7 ), and ex vivo studies using mouse hearts overexpressing Hsp-27 have demonstrated that it protects the myocardium against ischemia and reperfusion injury ( 8, 9 ). Further studies have demonstrated that Hsp-27 is expressed within human blood vessels ( 10 ) and phosphorylated Hsp-27 is believed to be protective against atherosclerosis ( 10–12 ).…”

mentioning

confidence: 99%

Heat Shock Protein-27 Delays Acute Rejection After Cardiac Transplantation

et al. 2014

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Increased Level of Hsp27 but Not of Hsp72 in Human Heart Allografts in Relation to Acute Rejection1

Abstract: For the first time in humans with cardiac allograft rejection, increased expression of HSP27, which could be important for cardiac self-protection, was demonstrated. For the lack of increased HSP72 expression, the influence of the cyclosporine A treatment was discussed.

Cited by 15 publications

References 10 publications

Heat Shock Protein 27 Is Associated With Freedom From Graft Vasculopathy After Human Cardiac Transplantation

Heat Shock Protein 27 Is Associated With Freedom From Graft Vasculopathy After Human Cardiac Transplantation

The role of heat shock protein 27 in bronchiolitis obliterans syndrome after lung transplantation

Heat Shock Protein-27 Delays Acute Rejection After Cardiac Transplantation

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