RT Journal Article
SR Electronic
T1 Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes
JF BMJ Open Diabetes Research & Care
JO BMJ Open Diab Res Care
FD American Diabetes Association
SP e002579
DO 10.1136/bmjdrc-2021-002579
VO 10
IS 1
A1 Xinyi Ding
A1 Chuzhen Meng
A1 Hangming Dong
A1 Shili Zhang
A1 Hui Zhou
A1 Wenchong Tan
A1 Lei Huang
A1 Aiping He
A1 Jieyou Li
A1 Jiali Huang
A1 Wei Li
A1 Fei Zou
A1 MengChen Zou
YR 2022
UL http://drc.bmj.com/content/10/1/e002579.abstract
AB 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.No data are available. The data generated and analyzed during the current study are available from the corresponding author upon reasonable request.