No replies to this topic

[Michael]

All:

Arterioscler Thromb Vasc Biol. 2011 May;31(5):1219-25. Epub 2011 Mar 3.
Circulating leukocyte and carotid atherosclerotic plaque telomere length: interrelation, association with plaque characteristics, and restenosis after endarterectomy.
Huzen J, Peeters W, de Boer RA, Moll FL, Wong LS, Codd V, de Kleijn DP, de Smet BJ, van Veldhuisen DJ, Samani NJ, van Gilst WH, Pasterkamp G, van der Harst P.


Shorter leukocyte telomeres are associated with atherosclerosis and predict future heart disease. The goal of the present study was to determine whether leukocyte telomere length is related to atherosclerotic plaque telomere length and whether it is associated with plaque characteristics or recurrence of disease.

METHODS AND RESULTS:
... [We compared] patients with carotid atherosclerosis undergoing carotid endarterectomy (n=684) and ... age- and gender-balanced subjects without clinical atherosclerosis (n=780). Leukocyte telomere length was shorter in patients versus controls (0.99 [interquartile range (IQR): 0.79 to 1.26] versus 1.06 [0.80 to 1.39]; P=0.0007) [as many others have also reported -MR]. Plaque telomeres were longer than leukocyte telomeres ... and independent of age. Leukocyte and plaque telomere length were only weakly correlated (correlation coefficient r2=0.04, P=0.03 [that's pretty damned weak! -MR]). Patients, whose plaques showed marked macrophage infiltration and large lipid core [ie, more severe atherosclerosis], had longer plaque telomeres (1.61 [IQR: 1.32 to 2.04] versus 1.40 [IQR: 1.15 to 1.57]; P=0.006) and shorter leukocyte telomeres (0.88 [IQR: 0.75 to 1.20] versus 1.03 [IQR: 0.83 to 1.34]; P=0.02). Plaque telomere length was associated with restenosis 1 year after endarterectomy (OR 1.58±0.206; P=0.026 per SD decrease of plaque telomere length). ...

This implies that the extrapolation of telomere length associations observed in leukocytes to that of the atherosclerotic vessel merits careful consideration. ... [T]he cells circulating leukocytes originate from are thought to divide far more frequently than vascular cells. Also specifically in carotid atherosclerotic plaques, a very long turnover time has recently been reported.²⁶ ... [As well,] the activity of [telomerase] differs between different types of tissue and in different situations.²⁷

In healthy rat carotid arteries, telomerase activity is barely detectable. However, after balloon injury [which mimics some aspects of the atherosclerotic insult -MR] there is a 10-fold increase of telomerase activity.²⁸ In patients with unstable angina, inflammatory cells present in the coronary artery plaque express considerably higher telomerase activity compared with circulating leukocytes.²⁹

Local leukocyte telomerase reactivation in plaques is thought to prolong the lifespan of inflammatory cells, which might make it possible to maintain the inflammatory response. This phenomenon could be an explanation for the longer plaque telomeres we found in inflammatory lipid-rich plaques, as well as for the lack of correlation of plaque telomere length with age [because the telomerase would be activated -- and telomeres would be lengthened -- as a response to the disease rather than as a function of age -MR]. ...

CONCLUSIONS:
Leukocyte telomere length is associated with the presence of atherosclerotic carotid plaques but is not a proxy for local plaque telomere length. Plaque telomere length is related to plaque characteristics and development of restenosis following endarterectomy.

PMID: 21372300

One possible implication could be that a telomerase-activating therapy could exacerbate the inflammatory environment in the plaque and increase vascular smooth muscle cell proliferation, making the plaque more severe and unstable.