Activation of the proapoptotic unfolded protein response in plaques of the human carotid artery.
Eur J Vasc Endovasc Surg
; 48(3): 248-57, 2014 Sep.
Article
in En
| MEDLINE
| ID: mdl-25060744
ABSTRACT
OBJECTIVE:
To analyze expression of keystone markers of apoptosis and the proapoptotic signaling pathway "unfolded protein response" (UPR) in rupture-prone plaques of the human carotid artery.METHODS:
Plaque specimens were obtained during endarterectomy for high-grade carotid stenosis, and were formalin-fixed. Ten specimens were identified that exhibited criteria of advanced rupture-prone atherosclerotic plaques, and histological and immunohistological analysis of markers of apoptosis (cleaved Caspase-3, TUNEL) and UPR (KDEL, ATF3, CHOP, CHAC-1) was performed. In addition, co-localization of apoptosis and UPR-activation was assessed by double-immunohistochemistry.RESULTS:
The mean size of the necrotic core was 44 ± 7% and the mean minimum/representative thicknesses of the fibrous cap were 129 ± 39 µm/280 ± 60 µm, respectively. Each specimen fulfilled at least two of the criteria for rupture-prone plaques. Semi-quantitative analysis of immunohistochemistry showed a significant increase in cleaved Caspase-3-positive (1923 ± 93 cells/mm(2)) and TUNEL-positive cells (1387 ± 66 cells/mm(2)) when compared with control tissue. Furthermore, expression of UPR-markers KDEL, AFT3 and CHOP was significantly increased (1175 ± 40 cells/mm(2), 1971 ± 69 cells/mm(2) and 2173 ± 120 cells/mm(2), respectively). Co-localization of UPR-activation with apoptosis was confirmed by double-immunohistochemistry, and lesional macrophages were identified as the primary cell-type involved.CONCLUSION:
For the first time, activation of the proapoptotic signaling pathway UPR has been identified in advanced rupture-prone plaques of the human carotid artery. This provides additional evidence for adding UPR to the potential targets for controlling plaque apoptosis and thereby preventing plaque progression/rupture.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arteriosclerosis
/
Carotid Arteries
/
Carotid Stenosis
/
Apoptosis
/
Unfolded Protein Response
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Eur J Vasc Endovasc Surg
Journal subject:
ANGIOLOGIA
Year:
2014
Document type:
Article