First, accumulating evidence has suggested that insufficient IGF-I levels play a role in vascular diseases, such as atherosclerosis and restenosis. Interestingly, atherosclerotic plaque involves many factors, and IGFs play a relevant role. Type I IGF receptors are present on smooth muscle cells, inflammatory cells, and arterial endothelial cells within the atherosclerotic lesion. Second, several in vitro studies have shown that IGF-I induces cell cycle changes resulting in VSMC proliferation and migration. VSMC apoptosis occurs in the evolutionary process of atherosclerotic plaques. It is likely that macrophage-derived IGF enhances cellular LDL uptake and degradation, as well as the macrophage cholesterol esterification rate. Third, atherosclerosis is characterized by a chronic lowgrade inflammatory state 32]. Recent studies have suggested that IGF-I exerts anti-inflammatory properties by decreasing the expression of pro-inflammatory cytokines. Conversely, Roubenoff et al. found a relationship between serum IGF-I and serum interleukin 6. In our study, we also found an inverse correlation between the levels of IGF-I and of Hs-CRP. Interestingly, the protective Procyanidin-B1 effect of IGF-I was found to be independent of inflammatory markers, either systemic or local. This suggests that the major effects of IGF-I are independent of inflammation control. Fourth, IGF-I plays a main role in restoring mitochondrial dysfunction during aging by increasing mitochondrial membrane potential, reducing oxygen consumption, and increasing ATP synthesis, which in turn minimize the cytochrome release to the cytoplasm and subsequently promote neural survival by decreasing caspaseinduced apoptosis. Azzouzi et al. confirmed the role of the IGF-I signaling pathway in the protection of cardiomyocytes under ischemic and hemodynamic loading conditions. Impaired IGF-I signaling has already been linked to increased oxidative stress and mitochondrial dysfunction in neuronal cells. Fifth, a number of studies have shown the importance of IGF-I in many processes of immune function. IGF-I plays important roles in T lymphocyte development and function. Specifically, it can increase the number of CD4+CD8+ immature T cells in rat thymus and spleen and promotes T cell survival. IGF-I has been reported to enhance IL-7-dependent B-cell proliferation in parallel with the c-kit ligand, as well as to potentiate IL-7 promotion of pro-B-cell expansion. Lastly, IGF-I penetrates into the brain and could potentially provide fast and efficient treatment to prevent chronic effects of stroke. IGF-I protects neurons against excitotoxicity and oxidative stress, as indicated by in vitro experiments showing that IGF-I inhibits glutamate-, Atractylenolide-III nitric oxide-, and hydrogen peroxide-induced apoptosis. IGF-I also protects oligodendrocyte precursors from cytotoxicity. In addition to having protective effects, IGF-I can also influence recovery from ischemic stroke through regeneration. Furthermore, it is able to modulate brain plasticity by influencing neurite outgrowth, synaptogenesis, neuronal excitability, and neurotransmi er release. Some limitations of this observational study merit consideration.