Carbon-14 Dating to Determine Carotid Plaque Age: Carbon-14 Dating of Carotid Plaques
(English)Manuscript (preprint) (Other academic)
Rationale: The exact nature of atherosclerotic plaque development and the molecular mechanisms that lead to clinical manifestations of carotid stenosis are unclear. After nuclear bomb tests in the 1950s, atmospheric 14C concentrations rapidly increased. Since then, the concentrations have been declining, and the curve of declination can be used to date biological samples synthesized during the last five to six decades.
Objective: To investigate plaque age as a novel characteristic of atherosclerotic plaques in patients with carotid stenosis.
Methods and Results: Carotid plaques from 29 well-characterized endarterectomy patients with symptomatic carotid stenosis were analyzed by accelerator mass spectrometry, and global gene expression of 25 plaque samples was profiled with HG-U133 Plus 2.0 arrays. The average plaque age was 9.3 years, and inter- and intrasample standard variations were low (1–3.5 years); thus, most of the plaques were generated 5–15 years before surgery. Plaque age was not associated with patient age or plaque size, determined by intima-media thickness, but was inversely related to plasma insulin levels (P=0.0014). A cluster of functionally related genes enriched with genes involved in immune responses was activated in plaques with low plaque age, as were oxidative phosphorylation genes.
Conclusion: Patients with mild insulin resistance have increased immune and inflammatory gene activity in their carotid plaques causing them to become instable, rapidly progressing into clinical manifestations at a relatively young age. These results show that plaque age, determined by 14C dating, is a novel and important characteristic of atherosclerotic plaques that will improve our understanding of the clinical significance and molecular underpinnings of atherosclerosis.
gene expression profiling, carotid stenosis, atherosclerosis, 14C dating, insulin resistance
Other Biological Topics
IdentifiersURN: urn:nbn:se:liu:diva-51917OAI: oai:DiVA.org:liu-51917DiVA: diva2:278120