IGF-1 and atherothrombosis: relevance to pathophysiology and therapy.
IGF-1 (insulin-like growth factor-1) plays a unique role in the cell protection of multiple systems, where its fine-tuned signal transduction helps to preserve tissues from hypoxia, ischaemia and oxidative stress, thus mediating functional homoeostatic adjustments. In contrast, its deprivation results in apoptosis and dysfunction. Many prospective epidemiological surveys have associated low IGF-1 levels with late mortality, MI (myocardial infarction), HF (heart failure) and diabetes. Interventional studies suggest that IGF-1 has anti-atherogenic actions, owing to its multifaceted impact on cardiovascular risk factors and diseases. The metabolic ability of IGF-1 in coupling vasodilation with improved function plays a key role in these actions. The endothelial-protective, anti-platelet and anti-thrombotic activities of IGF-1 exert critical effects in preventing both vascular damage and mechanisms that lead to unstable coronary plaques and syndromes. The pro-survival and anti-inflammatory short-term properties of IGF-1 appear to reduce infarct size and improve LV (left ventricular) remodelling after MI. An immune-modulatory ability, which is able to suppress 'friendly fire' and autoreactivity, is a proposed important additional mechanism explaining the anti-thrombotic and anti-remodelling activities of IGF-1. The concern of cancer risk raised by long-term therapy with IGF-1, however, deserves further study. In the present review, we discuss the large body of published evidence and review data on rhIGF-1 (recombinant human IGF-1) administration in cardiovascular disease and diabetes, with a focus on dosage and safety issues. Perhaps the time has come for the regenerative properties of IGF-1 to be assessed as a new pharmacological tool in cardiovascular medicine.
Cardiology Division, Department of Clinical and Molecular Medicine, II Faculty of Medicine of Rome Sapienza, Rome, Italy. elena.conti@uniroma1.it
Elena
E
Conti
Maria Beatrice
MB
Musumeci
Marco
M
De Giusti
Eleonora
E
Dito
Vittoria
V
Mastromarino
Camillo
C
Autore
Massimo
M
Volpe
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology* / Q000517:prevention & control; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy; D003920:Diabetes Mellitus / Q000188:drug therapy; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013927:Thrombosis / Q000503:physiopathology* / Q000517:prevention & control
D002317:Cardiovascular Agents; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I