title: Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.
abstract: BACKGROUND
  The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric (14)C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.
  
  
  RESULTS
  The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for (14)C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1-5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.
  
  
  CONCLUSIONS
  Our results show, for the first time, that plaque age, as judge by relative incorporation of (14)C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.
authors.affiliation: The Cardiovascular Genomics Group, Department of Medical Biochemistry and Biophysics, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Hägg
authors.forename: Mehran
authors.initials: M
authors.lastname: Salehpour
authors.forename: Peri
authors.initials: P
authors.lastname: Noori
authors.forename: Jesper
authors.initials: J
authors.lastname: Lundström
authors.forename: Göran
authors.initials: G
authors.lastname: Possnert
authors.forename: Rabbe
authors.initials: R
authors.lastname: Takolander
authors.forename: Peter
authors.initials: P
authors.lastname: Konrad
authors.forename: Stefan
authors.initials: S
authors.lastname: Rosfors
authors.forename: Arno
authors.initials: A
authors.lastname: Ruusalepp
authors.forename: Josefin
authors.initials: J
authors.lastname: Skogsberg
authors.forename: Jesper
authors.initials: J
authors.lastname: Tegnér
authors.forename: Johan
authors.initials: J
authors.lastname: Björkegren
mesh_terms: D000368:Aged; D002340:Carotid Artery Diseases / Q000097:blood* / Q000473:pathology*; D016893:Carotid Stenosis / Q000097:blood* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000473:pathology*
chemical_list: D007328:Insulin