(14-04-14) Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

Sara Hägg, Mehran Salehpour, Peri Noori, Jesper Lundström, Göran Possnert, Rabbe Takolander, Peter Konrad, Stefan Rosfors, Arno Ruusalepp, Josefin Skogsberg, Jesper Tegnér, Johan Björkegren mail

· Published: April 07, 2011
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 14C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.
Methodology/Principal Finding
The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for 14C 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/Significance
Our results show, for the first time, that plaque age, as judge by relative incorporation of 14C, 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.
Competing interests: The authors have declared that no competing interests exist. Clinical Gene Networks has nothing against PLoS ONE polices on sharing data and materials. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Source: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018248

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