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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

  • Helena Grauen Larsen
  • Goran Marinkovic
  • Peter M. Nilsson
  • Jan Nilsson
  • Gunnar Engström
  • Olle Melander
  • Marju Orho-Melander
  • Alexandru Schiopu
Publishing year: 2019
Language: English
Pages: 925-933
Publication/Series: Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 39
Issue: 5
Document type: Journal article
Publisher: Lippincott Williams Wilkins Hagerstown, MD

Abstract english

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.


  • Cardiac and Cardiovascular Systems
  • cardiovascular diseases
  • carotid artery disease
  • extracellular matrix metalloproteinase inducer
  • intima-media thickness
  • mortality
  • receptor for advanced glycation end products


  • Cardiovascular Research - Immunity and Atherosclerosis
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • ISSN: 1524-4636
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00