Heat Shock Proteins in Vascular Disease—A Review

Mehta, Tapan; Greenman, John; Ettelaie, Camille; Venkatasubramaniam, Arundhathi; Chetter, Ian; McCollum, P.T.

doi:10.1016/j.ejvs.2005.01.005

Cited by 64 publications

(63 citation statements)

References 62 publications

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“…18 Current evidence suggests that antibody titres to Hsps are elevated in patients with vascular disease, and that this is related to the severity of atherosclerosis. 19 In the current study, we have shown anti-Hsps are raised in obesity, in the absence of clinically evident coronary disease, but that they are not significantly raised in overweight subjects.…”

Section: Discussionmentioning

confidence: 43%

Association between indices of body mass and antibody titres to heat-shock protein-60, -65 and -70 in healthy Caucasians

et al. 2006

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We have previously shown that antibody titres to several heat-shock proteins (Hsps) are elevated in dyslipidaemic patients and subjects with established vascular disease. Obesity is known to be associated with raised serum inflammatory markers suggesting a state of heightened immune activation. Hence, we have investigated the association between indices of obesity and several Hsp antibody titres in healthy subjects. Subjects (n ¼ 170) were recruited from among employees at the University of Surrey and the Royal Surrey County Hospital, Guildford, UK. Of these subjects, 35 were obese with a body mass index (BMI)X30 kg/m 2 (19 male and 16 female subjects), 58 were overweight with 304BMIX25 kg/m 2 (36 male and 22 female subjects) and 77 were of a normal weight with BMIo25 kg/m 2 (31 male and 46 female subjects). Overall, obese subjects had significantly higher plasma anti-Hsp-60 (Po0.001), anti-Hsp-65 (Po0.05) and anti-Hsp-70 (Po0.05) compared with overweight and normal weight subjects.

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Section: Discussionmentioning

confidence: 43%

Association between indices of body mass and antibody titres to heat-shock protein-60, -65 and -70 in healthy Caucasians

et al. 2006

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“…Several studies have investigated the link between cardiovascular disease (CVD) and serum/plasma levels of HSP or HSP auto-antibodies. A clear link between HSP60 serum levels and CVD has been shown [17]. However, the connection between HSP70 or anti-HSP70 antibody levels and CVD or CVD risk phenotypes is unclear.…”

Section: Discussionmentioning

confidence: 99%

Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages

et al. 2006

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Lipid accumulation and inflammation are key hallmarks of the atherosclerotic plaque and macrophage uptake of oxidized low-density lipoprotein (oxLDL) is believed to drive these processes. Initial experiments show that supernatants from oxLDL treated macrophages could induce IL-1β production in naïve macrophages. To search for potential paracrine mediators that could mediate this effect a DNA microarray scan of oxLDL treated human macrophages was performed. This analysis revealed that oxLDL induced activation of heat shock protein (HSP) expression. HSPs have been implicated in the development of atherosclerosis, but the exact mechanisms for this is unclear. Extracellular heat shock protein 70 (HSP70) has been shown to elicit a pro-inflammatory cytokine response in monocytes and could therefore be a potential paracrine pro-inflammatory mediator. After 24 h of oxLDL treatment there was a significant increase of HSP70 concentrations in supernatants from oxLDL treated macrophages (oxLDLsup) compared to untreated controls (P < 0.05). OxLDLsup could induce both interleukin (IL)-1β and IL-12 secretion in naïve macrophages. We also demonstrate that the effect of oxLDLsup on cytokine production and release could be blocked by inhibition of HSP70 transcription or secretion or by the use of HSP70 neutralizing antibodies. This suggests that extracellular HSP70 can mediate pro-inflammatory changes in macrophages in response to oxLDL.

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“…Their primary function is to fulfill chaperoning activity: as new proteins are being produced by ribosomes, HSPs assist in correct folding of polypeptide chains into functional protein, and after a stress event, HSPs assist in refolding or degradation of damaged or denatured proteins (2 ).…”

confidence: 99%

Plasma Concentration of Heat Shock Protein 27 and Risk of Cardiovascular Disease: A Prospective, Nested Case-Control Study

et al. 2008

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Background: Heat shock protein 27 (HSP27) has been hypothesized to be a potential biomarker of atherothrombosis. However, no prospective studies have yet been performed to investigate the association between HSP27 plasma concentration and incident cardiovascular events among initially healthy individuals. Methods: We evaluated plasma concentrations of HSP27 at baseline among 255 initially healthy participants in the Women’s Health Study who subsequently developed myocardial infarction, ischemic stroke, or cardiovascular death during a follow-up period of up to 5.9 years and among an equal number of women matched for age and smoking but who remained free of cardiovascular disease over the same time period. Results: Overall, HSP27 plasma concentrations were inversely associated with age (Spearman correlation coefficient r = −0.258, P <0.001), but not with other established cardiovascular risk factors. Conditional logistic regression analysis showed no significant association of baseline HSP27 plasma concentration with future cardiovascular disease; the odds ratio for upper vs lower tertile of HSP27 concentration at baseline was 0.99 (95% CI 0.62–1.57, P for trend = 0.99). Conclusion: In this prospective study of initially healthy women, baseline HSP27 plasma concentration was not associated with incident cardiovascular events.

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Heat Shock Proteins in Vascular Disease—A Review

Cited by 64 publications

References 62 publications

Association between indices of body mass and antibody titres to heat-shock protein-60, -65 and -70 in healthy Caucasians

Association between indices of body mass and antibody titres to heat-shock protein-60, -65 and -70 in healthy Caucasians

Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages

Plasma Concentration of Heat Shock Protein 27 and Risk of Cardiovascular Disease: A Prospective, Nested Case-Control Study

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