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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

High Telomerase Activity in Neutrophils From Unstable Coronary Plaques

Maria Lucia Narducci, MD^_*,_*, Annalisa Grasselli, PhD^_*,¶, Luigi Marzio Biasucci, MD, FACC^_*, Antonella Farsetti, MD^||,¶, Antonino Mulè, MD, Giovanna Liuzzo, MD^_*, Giuseppe La Torre, MD, Giampaolo Niccoli, MD^_*, Rocco Mongiardo, MD^_*, Alfredo Pontecorvi, MD and Filippo Crea, MD, FACC^_*

^_* Institute of Cardiology
Division of Anatomic Pathology and Histology
Institute of Medical Pathology
Institute of Hygiene, Catholic University of Sacred Heart, Rome, Italy
^|| Neurobiology and Molecular Medicine Institute, National Council of Research, Rome, Italy
^¶ Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy

Manuscript received April 16, 2007; revised manuscript received August 6, 2007, accepted August 13, 2007.

^_* Reprint requests and correspondence: Dr. Maria Lucia Narducci, Institute of Cardiology, Largo "A. Gemelli" n.8, 00168 Rome, Italy (Email: lianarducci{at}yahoo.it).

Objectives: We evaluated telomerase activity in circulating polymorphonuclear neutrophils (PMN) and in PMN isolated from coronary atherosclerotic plaques by a novel approach.

Background: Delayed apoptosis of PMN have been demonstrated in unstable angina (UA). These cells have a finite lifespan with low telomerase activity, a polymerase that extends telomeres, structures essential for cell aging. Reactivation of telomerase has been associated with resistance to apoptosis.

Methods: We studied 20 patients with UA and 6 patients with chronic stable angina (SA), undergoing a percutaneous coronary intervention. Circulating PMN were isolated from venous blood and PMN derived from coronary plaque were isolated from washing medium of angioplasty balloons.

Results: Telomerase activity was higher in coronary plaque PMN of UA patients than in coronary plaque PMN of SA patients (122.7, range 20.5 to 3,696; and 47.7, range 16 to 212.6, respectively, p = 0.001) and higher than in peripheral PMN of SA patients (122.7, range 20.5 to 3,696 vs. 59, range 16.5 to 132.5, p = 0.001). We found a statistically significant difference between venous and coronary plaque PMN telomerase activity in UA patients (z = –2.875; p = 0.004). Among UA patients, a shorter time interval from symptom onset to coronary PMN sampling was the only independent predictor of high telomerase activity in coronary plaque PMN (p < 0.001, R² = 0.75).

Conclusions: In UA patients, telomerase activity is high in coronary plaque PMN, while it is low in peripheral PMN. Telomerase reactivation in resident PMN resulting in a prolonged lifespan might play a key role in the early phases of instability.

Abbreviations and Acronyms   DNA = deoxyribonucleic acid   PCI = percutaneous coronary intervention   PMN = polymorphonuclear neutrophils   SA = stable angina   TRAP = telomeric repeat amplification protocol   UA = unstable angina

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