DNA damage and repair in a model of rat vascular injury. Clinical science (London, England : 1979) [Clin Sci (Lond)] Journal article | | Title | DNA damage and repair in a model of rat vascular injury. | | Author(s) | Forte A, Finicelli M, Grossi M, Vicchio M, Alessio N, Santè P, De Feo M, Cotrufo M, Berrino L, Rossi F, Galderisi U, Cipollaro M | | Source | Clin Sci (Lond) 2009 Oct 5. | | Abstract | Restenosis rate following vascular interventions still limits their long-term success. Oxidative stress plays a relevant role in this pathophysiological phenomenon, but less attention has been devoted to its effects on DNA damage and to the subsequent mechanisms of repair. We analysed in a model of arteriotomy-induced stenosis in rat carotids the time-dependent expression of DNA damage markers and of DNA repair genes, together with the assessment of proliferation and apoptosis indexes. The expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'-deoxyguanosine was increased at 3 and 7 days after arteriotomy, with immunostaining distributed in the injured vascular wall and in perivascular tissue. The expression of the DNA damage marker phospho-H2A.X was less relevant but increasing from 4 hrs to 7 days after arteriotomy, with immunostaining prevalently present in the adventitia and, to a lesser extent, in medial smooth muscle cells at the injury site. RT-PCR indicated a decrease of 8 out of 12 genes of the DNA repair machinery we selected from 4 hrs to 7 days after arteriotomy with the exception of increased Muyth and Slk genes (p<0.05). Western Blot revealed a decrease of p53 and catalase at 3 days after arteriotomy (p<0.05). A maximal 7% of BrdU-positive cells in endothelium and media occurred at 7 days after arteriotomy, while the apoptotic index peaked at 3 days after injury (p<0.05). Our results highlight a persistent DNA damage presumably related to a temporary decreased expression of the DNA repair machinery and of the antioxidant enzyme catalase, playing a role in stenosis progression. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19804370 |
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