Dataset Information

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.

Methodology/principal finding

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/significance

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.

SUBMITTER: Hagg S

PROVIDER: S-EPMC3072386 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Publications

Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

Hägg Sara S Salehpour Mehran M Noori Peri P Lundström Jesper J Possnert Göran G Takolander Rabbe R Konrad Peter P Rosfors Stefan S Ruusalepp Arno A Skogsberg Josefin J Tegnér Jesper J Björkegren Johan J

PloS one 20110407 4

<h4>Background</h4>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 carot ...[more]

PMID: 21490968

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Project description:Background & aimsPlasma bile acids (BAs) have been extensively studied as pathophysiological actors in non-alcoholic steatohepatitis (NASH). However, results from clinical studies are often complicated by the association of NASH with type 2 diabetes (T2D), obesity, and insulin resistance (IR). Here, we sought to dissect the relationship between NASH, T2D, and plasma BA levels in a large patient cohort.MethodsFour groups of patients from the Biological Atlas of Severe Obesity (ABOS) cohort (Clinical Trials number NCT01129297) were included based on the presence or absence of histologically evaluated NASH with or without coincident T2D. Patients were matched for BMI, homeostatic model assessment 2 (HOMA2)-assessed IR, glycated haemoglobin, age, and gender. To study the effect of IR and BMI on the association of plasma BA and NASH, patients from the HEPADIP study were included. In both cohorts, fasting plasma BA concentrations were measured.ResultsPlasma BA concentrations were higher in NASH compared with No-NASH patients both in T2D and NoT2D patients from the ABOS cohort. As we previously reported that plasma BA levels were unaltered in NASH patients of the HEPADIP cohort, we assessed the impact of BMI and IR on the association of NASH and BA on the combined BA datasets. Our results revealed that NASH-associated increases in plasma total cholic acid (CA) concentrations depend on the degree of HOMA2-assessed systemic IR, but not on β-cell function nor on BMI.ConclusionsPlasma BA concentrations are elevated only in those NASH patients exhibiting pronounced IR.Lay summaryNon-alcoholic steatohepatitis (NASH) is a progressive liver disease that frequently occurs in patients with obesity and type 2 diabetes. Reliable markers for the diagnosis of NASH are needed. Plasma bile acids have been proposed as NASH biomarkers. Herein, we found that plasma bile acids are only elevated in patients with NASH when significant insulin resistance is present, limiting their utility as NASH markers.

Dataset Information

Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

Background

Methodology/principal finding

Conclusions/significance

Publications

Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

Similar Datasets

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