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High Plasma sRAGE (Soluble Receptor for Advanced Glycation End Products) Is Associated With Slower Carotid Intima-Media Thickness Progression and Lower Risk for First-Time Coronary Events and Mortality

Grauen Larsen, Helena LU ; Marinkovic, Goran LU ; Nilsson, Peter M. LU ; Nilsson, Jan LU ; Engström, Gunnar LU ; Melander, Olle LU ; Orho-Melander, Marju LU and Schiopu, Alexandru LU (2019) In Arteriosclerosis, Thrombosis, and Vascular Biology 39(5). p.925-933
Abstract

Objective- RAGE (receptor for advanced glycation end products) and EMMPRIN (extracellular matrix metalloproteinase inducer) are immune receptors for proinflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, possibly by acting as a decoy receptor for its ligands. Whether sEMMPRIN (soluble EMMPRIN) has similar roles is unknown. We hypothesized that sRAGE and sEMMPRIN might be associated with vascular disease progression, incident coronary events, and mortality. Approach and Results- We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free individuals from the population-based Malmö Diet and Cancer... (More)

Objective- RAGE (receptor for advanced glycation end products) and EMMPRIN (extracellular matrix metalloproteinase inducer) are immune receptors for proinflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, possibly by acting as a decoy receptor for its ligands. Whether sEMMPRIN (soluble EMMPRIN) has similar roles is unknown. We hypothesized that sRAGE and sEMMPRIN might be associated with vascular disease progression, incident coronary events, and mortality. Approach and Results- We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free individuals from the population-based Malmö Diet and Cancer cohort. Measurements of intima-media thickness in the common carotid artery were performed at inclusion and after a median of 16.5 years. sRAGE was negatively correlated with carotid intima-media thickness progression, independently of traditional cardiovascular risk factors, kidney function, and hsCRP (high sensitive C-reactive protein). Additionally, sRAGE was associated with decreased risk for major adverse coronary events (hazard ratio=0.90 [0.82-0.97]; P=0.009) and mortality (hazard ratio=0.93 [0.88-0.99]; P=0.011) during a follow-up period of 21 years. The relationship with mortality was independent of all considered potential confounders. We found no correlations between EMMPRIN, intima-media thickness progression, or prognosis. Conclusions- Individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression and a better prognosis. Although its predictive value was too weak to promote sRAGE as a useful clinical biomarker in the population, the findings support further research into the potential anti-inflammatory and atheroprotective properties of this soluble receptor.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cardiovascular diseases, carotid artery disease, extracellular matrix metalloproteinase inducer, intima-media thickness, mortality, receptor for advanced glycation end products
in
Arteriosclerosis, Thrombosis, and Vascular Biology
volume
39
issue
5
pages
9 pages
publisher
Lippincott Williams Wilkins Hagerstown, MD
external identifiers
  • scopus:85065217740
ISSN
1524-4636
DOI
10.1161/ATVBAHA.118.312319
language
English
LU publication?
yes
id
bb9d11ce-92f2-46ad-9fc3-a9eca26079a0
date added to LUP
2019-05-21 13:37:09
date last changed
2019-06-11 04:05:15
@article{bb9d11ce-92f2-46ad-9fc3-a9eca26079a0,
  abstract     = {<p>Objective- RAGE (receptor for advanced glycation end products) and EMMPRIN (extracellular matrix metalloproteinase inducer) are immune receptors for proinflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, possibly by acting as a decoy receptor for its ligands. Whether sEMMPRIN (soluble EMMPRIN) has similar roles is unknown. We hypothesized that sRAGE and sEMMPRIN might be associated with vascular disease progression, incident coronary events, and mortality. Approach and Results- We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free individuals from the population-based Malmö Diet and Cancer cohort. Measurements of intima-media thickness in the common carotid artery were performed at inclusion and after a median of 16.5 years. sRAGE was negatively correlated with carotid intima-media thickness progression, independently of traditional cardiovascular risk factors, kidney function, and hsCRP (high sensitive C-reactive protein). Additionally, sRAGE was associated with decreased risk for major adverse coronary events (hazard ratio=0.90 [0.82-0.97]; P=0.009) and mortality (hazard ratio=0.93 [0.88-0.99]; P=0.011) during a follow-up period of 21 years. The relationship with mortality was independent of all considered potential confounders. We found no correlations between EMMPRIN, intima-media thickness progression, or prognosis. Conclusions- Individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression and a better prognosis. Although its predictive value was too weak to promote sRAGE as a useful clinical biomarker in the population, the findings support further research into the potential anti-inflammatory and atheroprotective properties of this soluble receptor.</p>},
  author       = {Grauen Larsen, Helena and Marinkovic, Goran and Nilsson, Peter M. and Nilsson, Jan and Engström, Gunnar and Melander, Olle and Orho-Melander, Marju and Schiopu, Alexandru},
  issn         = {1524-4636},
  keyword      = {cardiovascular diseases,carotid artery disease,extracellular matrix metalloproteinase inducer,intima-media thickness,mortality,receptor for advanced glycation end products},
  language     = {eng},
  number       = {5},
  pages        = {925--933},
  publisher    = {Lippincott Williams  Wilkins Hagerstown, MD},
  series       = {Arteriosclerosis, Thrombosis, and Vascular Biology},
  title        = {High Plasma sRAGE (Soluble Receptor for Advanced Glycation End Products) Is Associated With Slower Carotid Intima-Media Thickness Progression and Lower Risk for First-Time Coronary Events and Mortality},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.118.312319},
  volume       = {39},
  year         = {2019},
}