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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, Catholic University of Sacred Heart, Rome, Italy
Division of Anatomic Pathology and Histology, Catholic University of Sacred Heart, Rome, Italy
Institute of Medical Pathology, Catholic University of Sacred Heart, Rome, Italy
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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