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 |
|
Related Article
-
Inside This Issue of JACC
J. Am. Coll. Cardiol. 2007 50: A27-A28.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
F. Cipollone, L. Felicioni, R. Sarzani, S. Ucchino, F. Spigonardo, C. Mandolini, S. Malatesta, M. Bucci, C. Mammarella, D. Santovito, et al.
A Unique MicroRNA Signature Associated With Plaque Instability in Humans
Stroke,
September 1, 2011;
42(9):
2556 - 2563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Huzen, W. Peeters, R. A. de Boer, F. L. Moll, L. S. M. Wong, V. Codd, D. P. V. de Kleijn, B. J. G. L. de Smet, D. J. van Veldhuisen, N. J. Samani, et al.
Circulating Leukocyte and Carotid Atherosclerotic Plaque Telomere Length: Interrelation, Association With Plaque Characteristics, and Restenosis After Endarterectomy
Arterioscler Thromb Vasc Biol,
May 1, 2011;
31(5):
1219 - 1225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. B. Segel, M. W. Halterman, and M. A. Lichtman
The paradox of the neutrophil's role in tissue injury
J. Leukoc. Biol.,
March 1, 2011;
89(3):
359 - 372.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Findeisen, F. Gizard, Y. Zhao, D. Cohn, E. B. Heywood, K. L. Jones, D. H. Lovett, D. A. Howatt, A. Daugherty, and D. Bruemmer
Telomerase Deficiency in Bone Marrow-Derived Cells Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation
Arterioscler Thromb Vasc Biol,
February 1, 2011;
31(2):
253 - 260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Gizard, E. B. Heywood, H. M. Findeisen, Y. Zhao, K. L. Jones, C. Cudejko, G. R. Post, B. Staels, and D. Bruemmer
Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages
Arterioscler Thromb Vasc Biol,
February 1, 2011;
31(2):
245 - 252.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. C. Yong, G. J. Pennings, M. Chang, A. Hamzah, T. Chung, M. Qi, D. Brieger, M. Behnia, S. A. Krilis, M. K. C. Ng, et al.
Intracoronary shear-related up-regulation of platelet P-selectin and platelet-monocyte aggregation despite the use of aspirin and clopidogrel
Blood,
January 6, 2011;
117(1):
11 - 20.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Libby and F. Crea
Clinical implications of inflammation for cardiovascular primary prevention
Eur. Heart J.,
April 1, 2010;
31(7):
777 - 783.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Biasucci, G. Liuzzo, R. Della Bona, M. Leo, S. Giubilato, and F. Crea
Cell survival: is not all about apoptosis: reply
Eur. Heart J.,
February 2, 2010;
31(4):
503 - 504.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Arruda-Olson, G. S. Reeder, M. R. Bell, S. A. Weston, and V. L. Roger
Neutrophilia Predicts Death and Heart Failure After Myocardial Infarction: A Community-Based Study
Circ Cardiovasc Qual Outcomes,
November 1, 2009;
2(6):
656 - 662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Biasucci, G. Liuzzo, S. Giubilato, R. Della Bona, M. Leo, M. Pinnelli, A. Severino, M. Gabriele, S. Brugaletta, M. Piro, et al.
Delayed neutrophil apoptosis in patients with unstable angina: relation to C-reactive protein and recurrence of instability
Eur. Heart J.,
September 2, 2009;
30(18):
2220 - 2225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Crea and F. Andreotti
The unstable plaque: a broken balance
Eur. Heart J.,
August 1, 2009;
30(15):
1821 - 1823.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Farsetti, A. Grasselli, S. Bacchetti, C. Gaetano, and M. C. Capogrossi
The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling
J Appl Physiol,
January 1, 2009;
106(1):
333 - 337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Biasucci, M. Leo, and G. L. De Maria
Local and Systemic Mechanisms of Plaque Rupture
Angiology,
August 1, 2008;
59(2_suppl):
73S - 76S.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. C. Sane
Telomerase-Positive Neutrophils: Plaque "Survivors" and Restenosis
J. Am. Coll. Cardiol.,
June 24, 2008;
51(25):
2443 - 2444.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Narducci, A. Grasselli, L. M. Biasucci, A. Farsetti, A. Mule, G. Liuzzo, G. Niccoli, R. Mongiardo, A. Pontecorvi, and F. Crea
Reply
J. Am. Coll. Cardiol.,
June 24, 2008;
51(25):
2444 - 2444.
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Spyridopoulos, Y. Erben, T. H. Brummendorf, J. Haendeler, K. Dietz, F. Seeger, C. K. Kissel, H. Martin, J. Hoffmann, B. Assmus, et al.
Telomere Gap Between Granulocytes and Lymphocytes Is a Determinant for Hematopoetic Progenitor Cell Impairment in Patients With Previous Myocardial Infarction
Arterioscler Thromb Vasc Biol,
May 1, 2008;
28(5):
968 - 974.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
