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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/H2850    most recent 01119.2003v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Torella, D. Articles by Chiariello, M. Search for Related Content PubMed PubMed Citation Articles by Torella, D. Articles by Chiariello, M.

Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury

¹Division of Cardiology and ²Division of Geriatrics, Federico II University, 80131 Naples; ³Department of Biological Chemistry, University of Catania, 95124 Catania; ⁴Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, 80131 Naples; ⁵Genecor Foundation, 80121 Naples; ⁶Division of Cardiology, Magna Græcia University, 88100 Catanzaro, Italy; and ⁷Research Institute for Human Development and Aging, Liverpool John Moores University, L3 2ET Liverpool, United Kingdom

Submitted 4 December 2003 ; accepted in final form 19 June 2004

Many older patients, because of their high prevalence of coronary artery disease, are candidates for percutaneous coronary interventions (PCI), but the effects of vascular aging on restenosis after PCI are not yet well understood. Balloon injury to the right carotid artery was performed in adult and old rats. Vascular smooth muscle cell (VSMC) proliferation, apoptotic cell death, together with Akt induction, telomerase activity, p27^kip1, and endothelial nitric oxide synthase (eNOS) expression was assessed in isolated arteries. Neointima hyperplasia and vascular remodeling along with endothelial cell regeneration were also measured after balloon injury. Arteries isolated from old rats exhibited a significant reduction of VSMC proliferation and an increase in apoptotic death after balloon injury when compared with 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 check points like telomerase activity and p27^kip1 expression were decreased and increased, respectively, compared with adults. After balloon injury, old rats showed a significant reduction of neointima formation and an increased vascular negative remodeling compared with 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 reendothelialization after balloon injury in aged animals. 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.

restenosis; Akt; cell cycle; nitric oxide

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