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FADD, Caspase-3, and Caspase-8 and Incidence of Coronary Events

Xue, Ling ; Borné, Yan LU ; Mattisson, Ingrid Yao LU ; Wigren, Maria LU ; Melander, Olle LU orcid ; Ohro-Melander, Marju ; Bengtsson, Eva LU orcid ; Fredrikson, Gunilla Nordin LU ; Nilsson, Jan LU and Engström, Gunnar LU (2017) In Arteriosclerosis, Thrombosis, and Vascular Biology 37(5). p.983-989
Abstract

OBJECTIVE: To investigate the relationship between 3 markers of apoptosis, that is, FADD (Fas-associated death domain-containing protein), caspase-3, and caspase-8, and incidence of coronary events (CEs) in a population-based cohort study.

APPROACH AND RESULTS: In vitro experiments were performed to assess the response of the apoptotic biomarkers after Fas stimulation of peripheral blood mononuclear cells. The experiments showed significantly increased releases of FADD, caspase-3, and caspase-8 after Fas stimulation. The relationship between FADD, caspase-3, and caspase-8, respectively, and incidence of CEs was studied in 4284 subjects from the population-based Malmö Diet and Cancer Study. Cox' proportional hazards regression was... (More)

OBJECTIVE: To investigate the relationship between 3 markers of apoptosis, that is, FADD (Fas-associated death domain-containing protein), caspase-3, and caspase-8, and incidence of coronary events (CEs) in a population-based cohort study.

APPROACH AND RESULTS: In vitro experiments were performed to assess the response of the apoptotic biomarkers after Fas stimulation of peripheral blood mononuclear cells. The experiments showed significantly increased releases of FADD, caspase-3, and caspase-8 after Fas stimulation. The relationship between FADD, caspase-3, and caspase-8, respectively, and incidence of CEs was studied in 4284 subjects from the population-based Malmö Diet and Cancer Study. Cox' proportional hazards regression was used to examine the association between the apoptotic biomarkers and incidence of CE over a mean follow-up of 19 years. A total of 381 individuals had CE during the follow-up. High FADD at baseline was significantly associated with incident CE. In the highest compared with the lowest quartile of FADD, the risk factor adjusted hazards ratio for CE was 1.82 (95% confidence interval, 1.35-2.46; P for trend <0.001). A significant association was also found between caspase-8 and CE; the hazards ratio (Q4 versus Q1) was 1.90 (95% confidence interval, 1.39-2.60; P for trend <0.001) after adjustment for risk factors. No association was found between caspase-3 and CEs.

CONCLUSIONS: High levels of FADD and caspase-8, but not caspase-3, were associated with increased incidence of CE in subjects from the general population. The in vitro experiments support the view that these biomarkers could reflect activation of the extrinsic apoptotic pathway.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apoptosis, Biomarkers/blood, Caspase 3/blood, Caspase 8/blood, Cells, Cultured, Coronary Disease/blood, Fas-Associated Death Domain Protein/blood, Female, Humans, Incidence, Leukocytes, Mononuclear/drug effects, Linear Models, Male, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Risk Factors, Sweden/epidemiology, Time Factors, Up-Regulation, fas Receptor/pharmacology
in
Arteriosclerosis, Thrombosis, and Vascular Biology
volume
37
issue
5
pages
7 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:28302628
  • scopus:85015665982
ISSN
1524-4636
DOI
10.1161/ATVBAHA.117.308995
language
English
LU publication?
yes
additional info
© 2017 American Heart Association, Inc.
id
dc5137f7-c8fd-4163-97ff-96a0a72c445b
date added to LUP
2019-03-07 10:27:06
date last changed
2024-06-25 07:51:12
@article{dc5137f7-c8fd-4163-97ff-96a0a72c445b,
  abstract     = {{<p>OBJECTIVE: To investigate the relationship between 3 markers of apoptosis, that is, FADD (Fas-associated death domain-containing protein), caspase-3, and caspase-8, and incidence of coronary events (CEs) in a population-based cohort study.</p><p>APPROACH AND RESULTS: In vitro experiments were performed to assess the response of the apoptotic biomarkers after Fas stimulation of peripheral blood mononuclear cells. The experiments showed significantly increased releases of FADD, caspase-3, and caspase-8 after Fas stimulation. The relationship between FADD, caspase-3, and caspase-8, respectively, and incidence of CEs was studied in 4284 subjects from the population-based Malmö Diet and Cancer Study. Cox' proportional hazards regression was used to examine the association between the apoptotic biomarkers and incidence of CE over a mean follow-up of 19 years. A total of 381 individuals had CE during the follow-up. High FADD at baseline was significantly associated with incident CE. In the highest compared with the lowest quartile of FADD, the risk factor adjusted hazards ratio for CE was 1.82 (95% confidence interval, 1.35-2.46; P for trend &lt;0.001). A significant association was also found between caspase-8 and CE; the hazards ratio (Q4 versus Q1) was 1.90 (95% confidence interval, 1.39-2.60; P for trend &lt;0.001) after adjustment for risk factors. No association was found between caspase-3 and CEs.</p><p>CONCLUSIONS: High levels of FADD and caspase-8, but not caspase-3, were associated with increased incidence of CE in subjects from the general population. The in vitro experiments support the view that these biomarkers could reflect activation of the extrinsic apoptotic pathway.</p>}},
  author       = {{Xue, Ling and Borné, Yan and Mattisson, Ingrid Yao and Wigren, Maria and Melander, Olle and Ohro-Melander, Marju and Bengtsson, Eva and Fredrikson, Gunilla Nordin and Nilsson, Jan and Engström, Gunnar}},
  issn         = {{1524-4636}},
  keywords     = {{Apoptosis; Biomarkers/blood; Caspase 3/blood; Caspase 8/blood; Cells, Cultured; Coronary Disease/blood; Fas-Associated Death Domain Protein/blood; Female; Humans; Incidence; Leukocytes, Mononuclear/drug effects; Linear Models; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Risk Factors; Sweden/epidemiology; Time Factors; Up-Regulation; fas Receptor/pharmacology}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{983--989}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Arteriosclerosis, Thrombosis, and Vascular Biology}},
  title        = {{FADD, Caspase-3, and Caspase-8 and Incidence of Coronary Events}},
  url          = {{http://dx.doi.org/10.1161/ATVBAHA.117.308995}},
  doi          = {{10.1161/ATVBAHA.117.308995}},
  volume       = {{37}},
  year         = {{2017}},
}