IGF-1 and atherothrombosis: relevance to pathophysiology and therapy

Abstract

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.

Insulin-like Growth Factor-1, Psoriasis, and Inflammation: A Ménage à Trois?

“…A number of epidemiological studies have suggested that IGF-I levels in the lower normal range are associated with an increased risk of ischemic heart disease, stroke, hypertension, reduced glucose tolerance, and diabetes (II, [21][22][23][24]. Although the relationship between IGF-I and cardiovascular disease is still unknown, a protective role in the development of atherosclerosis was suggested for free IGFI levels (24).…”

Endothelial cells and the IGF system

“…Endothelial progenitor cells (EPCs), which are derived from bone marrow or vessel walls, promote vessel repair and prevent endothelial dysfunction (Conti et al 2011, Higashi et al 2012. They may differentiate to form a new endothelium or act as paracrine sources of cytokines and growth factors to enhance endothelial repair.…”

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

“…Although IGF-I activity appears to play a pacesetter role in the aging process, and is sometimes referred to as a universal cancer promoter, it does however have a direct favorable impact on vascular endothelial function and endothelial precursor cells, and its dietary downregulation might therefore have a countervailing negative impact on vascular health (Perticone et al 2008;Csiszar et al 2008;Conti et al 2011;Devin and Young 2008)-an effect which might have a greater impact on health in aging humans than in rodents. It seems unlikely, however, that IGF-I's impact on the vasculature played an important role in the lower mortality associated with higher protein intakes among the elderly in the NHANES III analysis, as, among those over 65, plasma IGF-I levels did not differ significantly as a function of protein intake (Levine et al 2014).…”