title: Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury.
abstract: 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, p27kip1, 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 p27kip1 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.
authors.affiliation: Div. of Cardiology, Magna Graecia Univ., Via Tommaso Campanella, 115, 88100 Catanzaro, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.forename: Dario
authors.initials: D
authors.lastname: Leosco
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
authors.forename: Carmela
authors.initials: C
authors.lastname: Coppola
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Ellison
authors.forename: Viviana G
authors.initials: VG
authors.lastname: Russo
authors.forename: Michele
authors.initials: M
authors.lastname: Torella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.forename: Franco
authors.initials: F
authors.lastname: Rengo
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiariello
mesh_terms: D000375:Aging / Q000502:physiology*; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division; D004730:Endothelium, Vascular / Q000293:injuries / Q000473:pathology* / Q000502:physiology*; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D001120:Arginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt