Serum sclerostin level and its relation to subclinical atherosclerosis in subjects with type 2 diabetes

Shalash, Magui Abdel Moneim; Rohoma, Kamel Hemida; Kandil, Noha Said; Mohsen, Mohsen Ahmed Abdel; Taha, Aya Abdul Fattah

doi:10.1016/j.jdiacomp.2019.04.012

Cited by 14 publications

(10 citation statements)

References 44 publications

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“…15 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%

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%

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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“…[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.…”

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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“…Sclerostin is thus a powerful bone formation and mineralization inhibitor (30) . In diabetic and CKD patients, studies have found a link between serum sclerostin levels and the presence of atherosclerosis and atherosclerotic plaques (8,12,16) . The CIMT as measured using ultrasonography is an inexpensive, easily applied, reproducible, non-invasive indicator that can be used to evaluate the presence and extent of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…CIMT measurements were taken using the B mode of a Mindray DC-7 equipment (China) at the radiology clinic. The atherosclerosis cutoff value was 0.90 mm (16) .…”

Section: Carotid Intima Media Thickness Measurementmentioning

confidence: 99%

The Relationship between Serum Sclerostin Levels and Carotid Intima Media Thickness in Predialysis Chronic Kidney Disease

Demi̇rci̇¹,

Sevinç²

2021

The Egyptian Journal of Hospital Medicine

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Background: The most common cause of increased morbidity and death throughout the chronic kidney disease (CKD) process is atherosclerosis, which advances quickly and is linked to cardiovascular diseases (CVDs). Sclerostin levels in CKD and CVDs have a complicated connection. Objective: We examined the relationship between serum sclerostin levels and atherosclerosis in patients with stage 3, 4, or 5 CKD who were not receiving hemodialysis treatment. Patients and Methods: A total of 125 patients aged >18 years with CKD stage 3, stage 4 and non-dialysis stage 5 were enrolled in the study. Patients with obesity, uncontrolled hypertension, coronary artery disease, with active cancer or liver disease, malignant hematologic disorders, acute renal failure, acute or chronic infections, were excluded. As for the control group; healthy volunteers without any known illness, regular drug use, smoking, alcohol use, and obesity were recruited. Results: Study population was diagnosed as 39.2% with diabetes mellitus and 91.2% of patients with arterial hypertension. 54% of the patients were female. There was a positive correlation between serum sclerostin levels and carotid intima media thickness (CIMT). A negative correlation was found between serum sclerostin levels and GFR and 25-OH vitamin D levels. Sclerostin levels were found to be significantly higher in the group with high CIMT levels. There was no difference in terms of other parameters. Conclusion: Sclerostin levels were significantly higher in patients with abnormal CIMT independent of GFR, calcium, phosphorus and PTH values. This finding suggests that the serum sclerotin level can be used as a CVD marker in patients with CKD.

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Serum sclerostin level and its relation to subclinical atherosclerosis in subjects with type 2 diabetes

Cited by 14 publications

References 44 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

The Relationship between Serum Sclerostin Levels and Carotid Intima Media Thickness in Predialysis Chronic Kidney Disease

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