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Hypoxia/reperfusion predisposes to atherosclerosis

Surgical interventions on blood vessels bear a risk for intimal hyperplasia and atherosclerosis as a consequence of injury. A specific feature of intimal hyperplasia is the loss of vascular smooth muscle cell (VSMC) differentiation gene expression. We hypothesized that immediate responses following...

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Bibliographic Details
Published in:PloS one 2018-10, Vol.13 (10), p.e0205067-e0205067
Main Authors: Finsterwalder, Richard, Ganesan, Minu Karthika, Leb, Heide, Habertheuer, Andreas, Basílio, José, Lang, Irene, Krunic, Milica, Wiedemann, Dominik, Petzelbauer, Peter
Format: Article
Language:English
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Summary:Surgical interventions on blood vessels bear a risk for intimal hyperplasia and atherosclerosis as a consequence of injury. A specific feature of intimal hyperplasia is the loss of vascular smooth muscle cell (VSMC) differentiation gene expression. We hypothesized that immediate responses following injury induce vascular remodeling. To differentiate injury due to trauma, reperfusion and pressure changes we analyzed vascular responses to carotid artery bypass grafting in mice compared to transient ligation. As a control, the carotid artery was surgically laid open only. In both, bypass or ligation models, the inflammatory responses were transient, peaking after 6h, whereas the loss of VSMC differentiation gene expression persisted. Extended time kinetics showed that transient carotid artery ligation was sufficient to induce a persistent VSMC phenotype change throughout 28 days. Transient arterial ligation in ApoE knockout mice resulted in atherosclerosis in the transiently ligated vascular segment but not on the not-ligated contralateral side. The VSMC phenotype change could not be prevented by anti-TNF antibodies, Sorafenib, Cytosporone B or N-acetylcysteine treatment. Surgical interventions involving hypoxia/reperfusion are sufficient to induce VSMC phenotype changes and vascular remodeling. In situations of a perturbed lipid metabolism this bears the risk to precipitate atherosclerosis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0205067