© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Native and oxidized low density lipoproteins oppositely modulate the effects of insulin-like growth factor I on VSMC
aEndocrinology Division, Hospital Carlos III, Instituto de Salud Carlos III, Comunidad de Madrid, C/ Sinesio Delgado 10, Madrid 28029, Spain
bImmunology Division, Hospital Carlos III, Instituto de Salud Carlos III, Madrid 28029, Spain
cCentro de Investigaciones Biológicas, Instituto "Reina Sofía" de Investigaciones Nefrológicas, Consejo Superior de Investigaciones Científicas, Madrid 28006, Spain
dCentro Nacional de Investigaciónes Cardiovasculares, CNIC, Madrid 28029, Spain
* Corresponding author. Tel.: +34-91-453-2500x2736; fax: +34-91-733-6614. emelian.hciii{at}salud.madrid.org
Objective: Changes in the local expression and signaling activity of the insulin-like growth factor-I (IGF-I) axis regulate growth and survival of plaque-derived vascular smooth muscle cells (VSMC) and influence plaque fate. Recent evidence suggests that accumulation of low density lipoproteins (LDL) in VSMC during the progression of atherogenesis is linked to local changes in IGF-I signaling. We investigated the effects of LDL on the biological actions and downstream signaling pathways mediated by this growth factor in A10 VSMC. Methods and Results: We first characterized the effects of LDL on the proliferative and anti-apoptotic actions of IGF-I in A10 VSMC. Native LDL were mitogenic and synergistically enhanced DNA synthesis induced by IGF-I from 4-, 9- up to 7.8-fold, while having no effect on its anti-apoptotic actions. In contrast, oxidized LDL, at oxidation levels that did not modify these actions by themselves, significantly reduced the mitogenic and survival effects of IGF-I by 40% and 60%, respectively. These observations correlated with opposite changes exerted by native and oxidized LDL on the insulin receptor substrate-1 (IRS)-associated PI3 kinase/Akt response to IGF-I. The extracellular signal-regulated kinase (ERK) signaling response was not affected. Conclusions: Our study demonstrates a previously unidentified modulation of the actions of IGF-I on A10 VSMC by LDL, dependent on their extent of oxidative modification. Our findings suggest that the differential modulation of the PI3 kinase/Akt response to IGF-I play a pivotal role.
KEYWORDS Atherosclerosis; Growth factor; Lipoprotein; Signal transduction; Smooth muscle
Time for primary review 25 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. B. Allen, B. E. Capps, E. C. Miller, D. R. Clemmons, and L. A. Maile Glucose-Oxidized Low-Density Lipoproteins Enhance Insulin-Like Growth Factor I-Stimulated Smooth Muscle Cell Proliferation by Inhibiting Integrin-Associated Protein Cleavage Endocrinology, March 1, 2009; 150(3): 1321 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F LaBelle and T. N Tulenko LDL, IGF-1, and VSMC apoptosis: linking atherogenesis to plaque rupture in vulnerable lesions Cardiovasc Res, February 1, 2004; 61(2): 204 - 205. [Full Text] [PDF]
|
|