The atheroprotective properties of Hsp70: a role for Hsp70-endothelial interactions?

Pockley, A. Graham; Calderwood, Stuart K.; Multhoff, Gabriele

doi:10.1007/s12192-009-0113-1

Cited by 56 publications

(54 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This inhibition reduces the expression of pro-inflammatory cytokines regulated by NF-κB, such as TNF-α, IL-6, or IL-1β (De et al 2000;Pockley et al 2009). In this line, our data show that the exercise-induced decrease of TLR2 and TLR4 was inversely correlated with the increase of Hsp70 in PBMC.…”

Section: Discussionmentioning

confidence: 99%

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

Rodriguez‐Miguelez

Fernandez‐Gonzalo

Almar

et al. 2014

AGE

View full text Add to dashboard Cite

This study assessed the effects of a resistance exercise training program on the inflammatory response associated with Toll-like receptor (TLR) 2 and TLR4 signaling pathways in senior participants. Twenty-six healthy subjects (age, 69.5±1.3) were randomized to a training (TG; n=16) or a control (CG; n=10) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and levels of proteins involved in the TLR2, TLR4, and myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways were analyzed. The inflammatory status was evaluated through messenger RNA (mRNA) and protein content of interleukin (IL)-10 and tumor necrosis factor alpha (TNF-α) and plasma levels of C-reactive protein (CRP). After the 8-week resistance training, TLR2 and TLR4 protein expression was reduced in TG. MyD88, p65, phosphop38, TIR domain-containing adaptor inducing interferon (TRIF), IKKi/IKKε, phospho-interferon regulatory factor (IRF) 3, and phosho-IRF7 were also downregulated in TG after the intervention. The training program induced an increase of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Hsp70 and a reduction of Hsp60. While TNF-α mRNA and protein values remained unchanged in both TG and CG, IL-10 mRNA and protein content were upregulated in TG after the intervention. CRP values decreased in TG only. The increase in Hsp70 negatively correlated with TLR2 and TLR4 downregulation. These data suggest that resistance exercise may represent an effective tool to ameliorate the pro-inflammatory status of old participants through an attenuation of MyD88-dependent and MyD88-independent TLR2 and TLR4 signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

Rodriguez‐Miguelez

Fernandez‐Gonzalo

Almar

et al. 2014

AGE

View full text Add to dashboard Cite

show abstract

“…It is not clear, whether higher serum Hsp70 levels are a causative or an atheroprotective factor due to severe systemic calcification. Evidence suggests that soluble Hsp70 is likely to be involved in cytoprotection (Bielecka-Dabrowa et al 2009) due to the chronic stress of atherosclerosis (Pockley et al 2009). The significance of this inverse relation between Hsp70 and atherosclerosis remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Serum level of soluble Hsp70 is associated with vascular calcification

Krepuska¹,

Szeberin²,

Sótonyi³

et al. 2011

Cell Stress and Chaperones

View full text Add to dashboard Cite

It has been previously reported that serum levels of 70-kDa heat shock protein (Hsp70) are elevated in peripheral artery disease. The aim of the present study was to examine whether increased serum Hsp70 levels are related to the extent of arterial calcification and standard laboratory parameters of patients with peripheral artery disease, as well as to markers of inflammation (C-reactive protein), atherosclerosis (homocysteine), and calcification (fetuin-a). One hundred eighty chronic atherosclerotic patients with significant carotid stenosis and/or lower extremity vascular disease were enrolled in this crosssectional study. Systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima-media thickness (IMT), presence of calcification at the abdominal aorta, carotid and femoral bifurcations, and aortic and mitral cardiac valves). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes, and traditional risk factors for atherosclerosis were noted. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay. Standard laboratory parameters (clinical chemistry), C-reactive protein (CRP), and homocysteine levels were determined by an autoanalyzer using the manufacturer's kits. Fetuin-a levels were measured by radial immunodiffusion. Patients' median age was 64 (57-71) years, 69% were men, and 34.5% had diabetes. Serum heat shock protein 70 levels were significantly higher in patients with more severe arterial calcification (p< 0.02) and showed significant positive correlations with serum bilirubin (r=0.23, p=0.002) and homocysteine levels (r= 0.18, p=0.02). Serum Hsp70 did not correlate with body mass index, IMT, CRP, or fetuin-a levels in this cohort. Logistic regression analysis confirmed the association between sHsp70 and calcification score (OR, 2.189; CI, p=0.016) and this correlation remained significant (OR, 2.264; CI, 1.021-5.020, p=0.044) after the adjustment for age, sex, eGFR, smoking, CRP, and homocysteine levels. Our data show that serum Hsp70 levels correlate with the severity of atherosclerosis in patients with carotid artery disease and chronic lower limb ischemia. These data support a putative role for plasma Hsp70 in the development of arterial calcification. Nevertheless, further studies are required to investigate the usefulness of circulating Hsp70 level as a marker of atherosclerotic calcification.

show abstract

“…Second, HSP70 activation of the TLR4 ligand on CD4 1 CD25 1 T cells is attributed to an increase in suppressive activity of these T cells in atherosclerosis. 82,83 Furthermore, HSP70 has been indicated to have a negative feedback effect on NF-kB signaling activity. 84 HSP70 has also been demonstrated to switch off TNF receptor-associated factor 6.…”

Section: Mature B Cells Were Decreased In Mice Treated With 17-dmagmentioning

confidence: 99%

Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus

et al. 2012

View full text Add to dashboard Cite

Elevated expression of heat shock protein 90 (HSP90) has been found in kidneys and serum of systemic lupus erythematosus (SLE) patients and MRL/Mp-Fas lpr /Fas lpr (MRL/lpr) autoimmune mice. We investigated if inhibition of HSP90 would reduce disease in MRL/ lpr mice. In vitro, pretreatment of mesangial cells with HSP90 inhibitor Geldanamycin prior to immune-stimulation showed reduced expression of IL-6, IL-12 and NO. In vivo, we found HSP90 expression was elevated in MRL/lpr kidneys when compared to C57BL/6 mice and MRL/lpr mice treated with HSP90 inhibitor 17-DMAG. MRL/lpr mice treated with 17-DMAG showed decreased proteinuria and reduced serum anti-dsDNA antibody production. Glomerulonephritis and glomerular IgG and C3 were not significantly affected by administration of 17-DMAG in MRL/lpr. 17-DMAG increased CD8 1 T cells, reduced double-negative T cells, decreased the CD4/CD8 ratio and reduced follicular B cells. These studies suggest that HSP90 may play a role in regulating T-cell differentiation and activation and that HSP90 inhibition may reduce inflammation in lupus.

show abstract

The atheroprotective properties of Hsp70: a role for Hsp70-endothelial interactions?

Cited by 56 publications

References 108 publications

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

Serum level of soluble Hsp70 is associated with vascular calcification

Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus

Contact Info

Product

Resources

About