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Am J Physiol Heart Circ Physiol (July 1, 2004). doi:10.1152/ajpheart.01119.2003
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Submitted on December 4, 2003
Accepted on June 19, 2004

Aging Exacerbates Negative Remodeling And Impairs Endothelial Regeneration After Balloon Injury

Daniele Torella1, Dario Leosco2, Ciro Indolfi3*, Antonio Curcio3, Carmela Coppola1, Georgina M. Ellison4, Viviana G. Russo1, Michele Torella5, Giovanni Li Volti6, Franco Rengo2, and Massimo Chiariello1

1 Division of Cardiology, Federico II University, Naples, Italy
2 Division of Geriatrics, Federico II University, Naples, Italy
3 Division of Cardiology, Magna Graecia University, Catanzaro, Italy
4 Department of Biological Chemistry, University of Catania, Catania, Italy
5 Research Institute for Human Development and Aging, Liverpool John Moores University, Liverpool, United Kingdom
6 Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy

* To whom correspondence should be addressed. E-mail: indolfi{at}unicz.it.

Background Many older patients, because of their high prevalence of coronary artery disease, are candidates for PCI, but the effects of vascular aging on restenosis after PCI are not yet well understood. Methods Balloon injury to the right carotid artery was performed in adult and old rats. VSMC proliferation, apoptotic cell death, together with Akt induction, telomerase activity, p27kip1and eNOS expression was assessed in isolated arteries. Neointima hyperplasia and vascular remodeling along with endothelial cell regeneration were also measured after balloon injury. Results Arteries isolated from old rats exhibited a significant reduction of VSMC proliferation and an increase in apoptotic death after balloon injury, when compared to adult rats. In the vascular wall of adult rats, balloon dilation induced Akt phosphorylation, and this was barely present in old rats. In arteries from old rats, Akt-modulated cell-cycle checkpoints like telomerase activity and p27kip1 expression were decreased and increased, respectively, when compared to adults. After balloon injury, old rats showed a significant reduction of neointima formation and an increased vascular negative remodeling, compared to adults. These results were coupled by a marked delay in endothelial regeneration in aged rats, partially mediated by a decreased eNOS expression and phosphorylation. Interestingly, chronic administration of L-Arginine prevented negative remodeling and improved re-endothelialization after balloon injury in aged animals. Conclusions A decreased neointimal proliferation, an impaired endothelial regeneration and an increase in vascular remodeling after balloon injury were observed in aged animals. The molecular mechanisms underlying these responses seem to be a reduced Akt and eNOS activity.




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