Insulin-like growth factor II and its receptors in atherosclerosis and in conditions predisposing to atherosclerosis.
OBJECTIVE
Growth factors regulate cellular migration, proliferation, and the production of extracellular matrix during the development of the atherosclerotic lesion. Here we discuss experimental evidence pointing to insulin-like growth factor II and its receptors as important players in cardiovascular diseases.


RESULTS
Genetically modified mice with altered levels of insulin-like growth factor II or receptors mediating insulin-like growth factor II signalling showed abnormalities known to be associated with, or contribute to, ageing and atherosclerosis in humans. These animal models displayed abnormalities in the morphology of the aortic tissue, glucose tolerance, response to oxidative stress and life span. Furthermore, human population studies showed a significant association between polymorphisms in the insulin-like growth factor II gene and obesity, a major risk factor for atherosclerosis.


CONCLUSIONS
Direct and indirect evidence in animal models points to insulin-like growth factor II and its signalling receptors as crucial players in atherosclerosis and in the onset of conditions predisposing to the disease. Furthermore, human population studies have established significant associations between specific polymorphisms at the insulin-like growth factor II gene and obesity which is an important risk factor for atherosclerosis. Future investigations should aim at understanding the molecular mechanisms underlying these effects and elucidating the potential role of the type 2 insulin-like growth factor receptor in the development of atherosclerotic lesions.
D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D017539:Tunica Intima / Q000378:metabolism
D006133:Growth Substances; D017451:Receptors, Somatomedin; D007335:Insulin-Like Growth Factor II