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.


OBJECTIVE
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.
Cittadini
A
A
Department of Internal Medicine, University Federico II, Naples, Italy.
Monti
M G
MG
Castiello
M C
MC
D'Arco
E
E
Galasso
G
G
Sorriento
D
D
Saldamarco
L
L
De Paulis
A
A
Napoli
R
R
Iaccarino
G
G
Saccà
L
L
D000818:Animals; D020212:Carotid Artery Injuries; D016893:Carotid Stenosis; D002404:Catheterization / Q000009:adverse effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology*; D007334:Insulin-Like Growth Factor I; D020011:Protective Agents; D051381:Rats; D012038:Regeneration; D017539:Tunica Intima; D017540:Tunica Media
D020011:Protective Agents; D007334:Insulin-Like Growth Factor I