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Contribution of Endoplasmic Reticulum Stress to the Clinical Instability of Carotid Plaques in Human Carotid Stenosis
- Source :
- Translational Stroke Research. 13(3):420-431
- Publication Year :
- 2022
- Publisher :
- Springer, 2022.
-
Abstract
- Endoplasmic reticulum (ER) stress is an important process during the progression of atherosclerosis. The aim of this study was to elucidate the association of ER stress and clinical instability of carotid plaque. One hundred ninety-three patients with carotid stenosis undergoing carotid endarterectomies (CEAs) were enrolled. We classified the patients into 3 groups: the asymptomatic, symptomatic, and cTIA (crescendo transient ischemic attack)/SIE (stroke in evolution) groups. Immunohistological staining was performed to assess ER stress and apoptosis. The correlation between ER stress marker expression and clinical instability was analyzed by Tukey–Kramer test and ordinal logistic regression. From the 193 CEAs, 24 asymptomatic plaques and 24 symptomatic plaques were randomly selected, and all 7 plaques in the cTIA/SIE group were selected. Glycophorin A staining demonstrated significant correlation between intraplaque hemorrhage and clinical instability (odds ratio [OR], 1.27; 95%CI, 1.14–1.41). The expression of ER stress markers (glucose-regulated protein 78 [GRP78] and C/EBP homologous protein [CHOP]) exhibited a significant correlation with clinical instability (GRP78: OR, 1.25; 95%CI, 1.14–1.38, CHOP: OR, 1.39; 95%CI, 1.16–1.66). Double-label immunofluorescence demonstrated ER stress markers were detected in CD68-positive cells and smooth muscle actin (SMA)-positive cells. The coexpression of the ER stress markers exhibited a significant correlation with clinical instability (CD68/GRP78: OR, 1.13; 95%CI, 1.05–1.20, CD68/CHOP: OR, 1.092; 95%CI, 1.04–1.14, SMA/CHOP: OR, 1.082; 95%CI, 1.04–1.13). However, the colocalization of CHOP and cleaved caspase-3 (apoptosis marker) did not correlate with clinical instability. These findings indicated that the ER stress pathway may be a potential therapeutic target in the prevention of stroke.
- Subjects :
- GRP78
Pathology
medicine.medical_specialty
Apoptosis
CHOP
Asymptomatic
medicine
Carotid stenosis
Humans
Stroke
Atherosclerotic plaque
Endarterectomy, Carotid
business.industry
CD68
General Neuroscience
Endoplasmic reticulum
Colocalization
medicine.disease
Atherosclerosis
Stenosis
Unfolded protein response
Endoplasmic reticulum stress
Neurology (clinical)
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Biomarkers
Transcription Factor CHOP
Subjects
Details
- Language :
- English
- ISSN :
- 18684483
- Volume :
- 13
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Translational Stroke Research
- Accession number :
- edsair.doi.dedup.....375086a460d257ad4112916b28f95b2b