Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study

Wang, Xinru; Shi, Jie; Lü, Bin; Zhang, Weiwei; Yang, Yehong; Wen, Jie; Hu, Renming; Yang, Zhen; Wang, Xuanchun

doi:10.1186/s12872-020-01456-7

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…16 Recent studies have reported several potential serum markers for screening of diabetic vascular complications, such as serum fibroblast growth factor 23, 17 serum sclerostin, 18 and circulating Hsp27. 19 In addition, heat shock proteins (HSPs) can be transported to the plasma membrane and released extracellularly, resulting in detectable levels of HSP in the blood. This finding has prompted clinical studies exploring the potential use of HSP and anti-HSP antibodies as serum biomarkers for DM complications.…”

Section: Discussionmentioning

confidence: 99%

“…However, fewer than 10% of patients have typical clinical symptoms and the lack of effective treatments affects patients’ prognoses 16. Recent studies have reported several potential serum markers for screening of diabetic vascular complications, such as serum fibroblast growth factor 23,17 serum sclerostin,18 and circulating Hsp27 19. In addition, heat shock proteins (HSPs) can be transported to the plasma membrane and released extracellularly, resulting in detectable levels of HSP in the blood.…”

Section: Discussionmentioning

confidence: 99%

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Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes

Ding

Meng

Dong

et al. 2022

BMJ Open Diab Res Care

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IntroductionAtherosclerosis is the main pathological change in diabetic angiopathy, and vascular inflammation plays an important role in early atherosclerosis. Extracellular heat shock protein 90 (eHsp90) is secreted into the serum and is involved in various physiological and pathophysiological processes. However, the specific mechanism of eHsp90 in early atherosclerosis remains unclear. This study explored the relationship between Hsp90 and diabetic lower extremity arterial disease and investigated the expression of eHsp90 in vascular endothelial cells under environmental stimulation and the function and mechanism of eHsp90α involved in diabetic atherosclerosis.Research design and methodsOne hundred and three selected patients were divided into three groups: the diabetes mellitus group (n=27), the diabetic lower extremity arterial disease group (n=46), and the diabetic critical limb ischemia group (n=30). The relationships among serum Hsp90, oxidative stress indexes, and patient outcomes and the correlations among the indexes were analyzed. H&E staining and immunohistochemistry were used to observe the vasculature of amputated feet from patients with diabetic foot. An oxidative stress endothelial injury model was established under high glucose in vitro to explore the role of eHsp90 release in atherosclerosis progression.ResultsThe level of serum Hsp90 was upregulated with aggravation of diabetic vascular disease. Hsp90α was correlated with malondialdehyde to some extent and was an independent risk factor in the progression of diabetic vascular disease, with predictive ability. The expression area of Hsp90α was consistent with the area of inflammatory infiltration in the vessel lumen. Vascular endothelial cells were found to increase eHsp90α secretion under stress. Then inhibition of eHsp90α can reduce the degree of cellular inflammation and damage. Endothelial cell-conditioned medium and recombinant human Hsp90α increased monocyte migration via the low-denisity lipoprotein receptor-related protein 1 (LRP1) receptor to promote disease progression.ConclusionseHsp90α plays a critical role in the early inflammatory injury stage of atherosclerosis.Trial registration numberNCT04787770.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes

Ding

Meng

Dong

et al. 2022

BMJ Open Diab Res Care

View full text Add to dashboard Cite

show abstract

“…[16] Recent studies have reported several potential serum markers for the screening of diabetic vascular complications, such as CD36, YKL-40, [17] hepatocyte growth factor, [18] serum broblast growth factor 23, [19] serum sclerostin, [20] serum growth differentiation factor 15, [21] and circulating Hsp27. [22] In addition, heat shock proteins (HSPs) can be transported to the plasma membrane and released extracellularly, resulting in detectable levels of HSPs in the blood. This nding has prompted clinical studies exploring the potential use of HSPs and anti-HSP antibodies as serum biomarkers for DM complications.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Hsp90α is a Potential Serum Predictor of Atherosclerosis in type 2 Diabetes

Ding

Meng

Dong

et al. 2021

Preprint

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Background: Atherosclerosis is the main pathological change in diabetic angiopathy, and vascular inflammation plays an important role in early atherosclerosis. Heat shock protein 90, a cellular molecular chaperone, was recently determined to be secreted extracellularly, but the specific mechanism remains unclear. This study explored the relationship between Hsp90 and diabetic peripheral artery disease through serological analyses of different groups of diabetic patients and investigated the relationship between extracellular Hsp90α and vascular inflammation at the cellular level.Methods: Seventy-seven selected patients were divided into three groups. The relationships among serum Hsp90, oxidative stress indexes and patient outcomes and the correlations among the indexes were analysed. An oxidative stress endothelial injury model was established under high glucose in vitro to explore the role of eHsp90 release in atherosclerosis progression.Results: Serum Hsp90 and MDA levels tended to increase in different groups with peripheral vascular disease aggravation. Hsp90α was correlated with MDA to some extent and was predictive. In vitro, high glucose and low H2O2 treatment increased extracellular Hsp90 secretion, and endothelial cell conditioned medium and recombinant human Hsp90α increased monocyte migration (P<0.05).Conclusions: Extracellular Hsp90α participates in endothelial cell injury in diabetic vascular disease and initiates the inflammatory response by promoting monocyte migration.Trial registration: NCT04787770, ClinicalTrials.gov, Registered 9 March, 2021 - Prospective registered

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“…In the retina, HSP27 may play a role as an endothelial barrier in conjunction with a general anti-apoptotic protein since downregulation of HSP27 in retinal capillary endothelial cells may lead to a vulnerable environment and increase apoptosis [ 26 ]. Elsewhere, HSP27 has been proposed as a vital protective factor in atherosclerosis [ 27 ]. Given that vascular dysregulation is a possible systemic risk factor for glaucoma, this may be an important finding by which to limit development or progression of glaucoma [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Thermal Injury Induces Small Heat Shock Protein in the Optic Nerve Head In Vivo

Kim

Park

2021

Korean J Ophthalmol

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To investigate the induction pattern of various heat shock protein (HSP) in the optic nerve head after thermal stress using transpupillary thermotherapy (TTT) and to determine the dose-response relationship of thermal stress on the induction of various HSP. Methods:The 810 nm diode laser with 50 um spot size was aimed to the center of optic nerve head of right eye of Norway brown rats. First, the various exposure powers (100, 120, 140mW) were used with the same exposure duration, 60 seconds, to investigate power dosing effect. Second, the various exposure durations (1, 2, 3, and 5 minutes) were applied under constant 100mW laser power to investigate time dosing effect. Left eyes were served as controls. To quantify HSP expression, enucleation was performed at 24 hours after TTT. HSP 27 and αB-crystallin inductions in optic nerve head were examined with Western blot.Results: All type of HSP was observed in normal state. After thermal injury, the expression of HSP 27 were increased, and the αB-crystallin were decreased.Conclusions: Induction pattern of each HSP in the optic nerve head were different after thermal injury. Some HSPs were induced or exhausted. Further research is needed on the characteristic functions and induction conditions of each HSP.

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Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study

Cited by 11 publications

References 30 publications

Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes

Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes

Extracellular Hsp90α is a Potential Serum Predictor of Atherosclerosis in type 2 Diabetes

Thermal Injury Induces Small Heat Shock Protein in the Optic Nerve Head In Vivo

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