IGF-1, oxidative stress and atheroprotection

Abstract

Atherosclerosis is a chronic inflammatory disease in which early endothelial dysfunction and subintimal modified lipoprotein deposition progress to complex, advanced lesions that are predisposed to erosion, rupture and thrombosis. Oxidative stress plays a critical role not only in initial lesion formation but also in lesion progression and destabilization. While growth factors are thought to promote vascular smooth muscle cell proliferation and migration, thereby increasing neointima, recent animal studies indicate that IGF-1 exerts pleiotropic anti-oxidant effects along with anti-inflammatory effects that together reduce atherosclerotic burden. This review discusses the effects of IGF-1 in vascular injury and atherosclerosis models, emphasizing the relationship between oxidative stress and potential atheroprotective actions of IGF-1.

Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study

“…IGF-1 enhances NO production by increasing endothelial NO synthase. IGF-1 also upregulates anti-oxidant enzymes [29]. Additionally, Thum T et al [30] reported that IGF-1 in response to GH administrarion elevated circulating endothelial progenitor cell levels associated with increased NO bioavailability, thereby preventing endothelial function.…”

Endothelial cells and the IGF system

“…GH-deficient patients with low IGF1 levels had impaired flow-mediated arterial dilation, which was endothelium dependent and NO mediated (Higashi et al 2010). In untreated hypertensive adults, low plasma IGF1 levels were associated with reduced endothelial function as measured by acetylcholine (ACh)-stimulated forearm blood flow; by contrast, there was no correlation with endothelium-independent, sodium nitroprusside-induced vasodilation (Perticone et al 2008).…”

IGF-1 levels are significantly correlated with patient-reported measures of sexual function

“…27 GH and IGF-1 have also been shown to have antioxidant and anti-inflammatory effects in animal models, suggesting a protective role for GH/ IGF-1 in vascular disease given the role of oxidative stress in initiating lipid-lesion formation as well as in the destabilization and progression of these lesions. 36 Interestingly, our data link IGF-1 levels to hyperlipidemia, highlighting a potential interplay between serum lipids and GH/IGF-1 levels. Although it is tempting to hypothesize that this correlation may indicate a response by the GH axis to hyperlipidemia, additional analysis is necessary to fully elucidate this.…”