Key result
Elevated serum Hsp90α is linked to diabetic vascular progression and identifies lower extremity disease with ~0.70 AUC.
Why the study?
The specific mechanism of extracellular Hsp90 in early atherosclerosis in type 2 diabetes remains unclear.
Cross-Sectional (n=103)
No
Effect estimate: AUC 0.701
Should not yet change diabetic vascular monitoring; leaves open prospective validation of Hsp90α as a progression biomarker.
INTRODUCTION: Atherosclerosis 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 METHODS: One 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. RESULTS: The 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. CONCLUSIONS: eHsp90α plays a critical role in the early inflammatory injury stage of atherosclerosis. TRIAL REGISTRATION NUMBER: NCT04787770.
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Ding et al. (2022) conducted a cross-sectional in Type 2 diabetes mellitus with or without lower extremity arterial disease (n=103). Serum Hsp90α vs. Patients with T2DM without lower extremity arterial disease was evaluated on Diagnostic efficacy of Hsp90α for diabetic lower extremity arterial disease (AUC 0.701). Elevated serum Hsp90α is an independent risk factor for diabetic vascular disease progression and distinguishes diabetic lower extremity arterial disease with an AUC of 0.701.
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