Dating Components of Human Atherosclerotic Plaques

Rationale: Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. Objective: In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s. Methods and Results: Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4 +/- 3.2 years, which was significantly lower than that of the shoulder region (12.9 +/- 3.0 years, P<0.01), the interface toward the media (12.4 +/- 3.3 years, P<0.01), and the core (9.8 +/- 4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation. Conclusions: These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials. (Circ Res. 2010; 106: 1174-1177.)