Increased Serum Levels of Heat Shock Protein 70 Are Associated With Low Risk of Coronary Artery Disease

Zhu, Jianhui; Quyyumi, Arshed A.; Wu, Hongsheng; Csákó, György; Rott, David; Zalles-Ganley, Alexandra; Ogunmakinwa, Jibike; Halcox, Julian; Epstein, Stephen E.

doi:10.1161/01.atv.0000074899.60898.fd

Cited by 175 publications

(130 citation statements)

References 31 publications

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“…A soluble heat-shock-mediated component to cardiovascular disease has been suggested by a number of studies. Previous works have shown an inverse correlation between circulating Hsp70 levels and atherosclerotic disease progression in cardiac (Zhu et al 2003;Zhang et al 2010) and in extracardiac vascular calcifications, such as peripheral artery disease of the lower extremities and carotid artery disease (Wright et al 2000;Martin-Ventura et al 2007). In their elegant study, Martin-Ventura et al (2007) showed significantly decreased Hsp70 levels in plasma of patients with CAD in relation to matched healthy subjects.…”

Section: Discussionmentioning

confidence: 95%

Serum level of soluble Hsp70 is associated with vascular calcification

Krepuska¹,

Szeberin²,

Sótonyi³

et al. 2011

Cell Stress and Chaperones

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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.

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Section: Discussionmentioning

confidence: 95%

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

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“…[14][15][16][17] It has been reported that anti-Hsp-70 titres are not elevated in subjects with severe coronary atherosclerosis, whereas titres to Hsp-60 and -65 were significantly raised in these patients. 15,17 It has also been reported that patients with type 2 diabetes mellitus have significantly higher anti-Hsp titres compared with non-diabetic controls. 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.…”

Section: Discussionmentioning

confidence: 97%

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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“…However, the connection between HSP70 or anti-HSP70 antibody levels and CVD or CVD risk phenotypes is unclear. Low serum levels of HSP70 has been associated with atherosclerosis in subjects with established hypertension [18] and coronary artery disease [19]. However, patients with intermittent claudication, critical lower limb ischaemia, aneurysms [20], hypertension [21] and cerebral ischemia [22] have elevated anti-HSP70 antibody levels.…”

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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Increased Serum Levels of Heat Shock Protein 70 Are Associated With Low Risk of Coronary Artery Disease

Cited by 175 publications

References 31 publications

Serum level of soluble Hsp70 is associated with vascular calcification

Serum level of soluble Hsp70 is associated with vascular calcification

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

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