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Insulin‐like growth factor‐1 protects from vascular stenosis and accelerates re‐endothelialization in a rat model of carotid artery injury
Background: IGF‐1 is a potent mitogen for vascular smooth muscle cells, but exerts protective effects on endothelial cells that may trigger antiatherogenic mechanisms. Objectives: This study was designed to test the hypothesis that an IGF‐1 excess following arterial injury prevents neointima formati...
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Published in: | Journal of thrombosis and haemostasis 2009-11, Vol.7 (11), p.1920-1928 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background: IGF‐1 is a potent mitogen for vascular smooth muscle cells, but exerts protective effects on endothelial cells that may trigger antiatherogenic mechanisms. Objectives: This study was designed to test the hypothesis that an IGF‐1 excess following arterial injury prevents neointima formation and vascular stenosis. Methods: Rats were subjected to carotid balloon injury and treated with IGF‐1 (1.2 mg kg−1 per die) or saline for 10 days. Results: In IGF‐1 treated animals, high tissue levels of eNOS, Akt and its phosphorylated form were found, confirming activation of IGF‐1‐dependent signaling pathways. IGF‐1 markedly reduced neointima formation and post‐injury arterial stenosis. IGF‐1 exerted proliferative and anti‐apoptotic effects in the media of injured carotids, but inhibited mitotic activity and induced apoptosis in the neointima. Furthermore, IGF‐1 stimulated mobilization of progenitor endothelial cells and re‐endothelialization of the injured arteries. L‐NAME administration inhibited IGF‐1 vasculoprotective effects. Conclusions: IGF‐1 attenuates post‐injury carotid stenosis by exerting differential effects in the neointima and tunica media with regard to the key components of the response to injury. The data point to a novel role of IGF‐1 as a potent vasculoprotective factor. |
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ISSN: | 1538-7933 1538-7836 1538-7836 |
DOI: | 10.1111/j.1538-7836.2009.03607.x |