Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

Abstract

BackgroundThe 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 FindingThe 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/SignificanceOur 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.

Accelerator mass spectrometry of ultra-small samples with applications in the biosciences

“…Furthermore, the plaque age was shown to be independent of patient age but related to the insulin level in the blood plasma. The original findings have been reported [18] and studies are planned with a larger population to include other environmental factors that could influence the plaque buildup.…”

Small sample Accelerator Mass Spectrometry for biomedical applications

“…Other examples of biological applications that have been reported during the last decade have involved bomb-peak dating of various biological samples, including dating of composite samples such as human plaques [4], teeth [5], fat [6] or highly purified DNA samples of human brain or heart for measuring the regeneration rates of specific cells [7][8][9].…”

Cerebral Aneurysms: Formation, Progression, and Developmental Chronology

“…58–63 Proteins and lipids have been dated to assess turnover and growth of pathological structures. 56, 57, 64 …”