AR, IGF-IR, IR and Peripheral Artery Disease (ANIMALPAD)

Peripheral artery disease (PAD) of lower limbs is one of the most common clinical manifestation of atherosclerosis and can be considered a major cardiovascular disease with important morbidity and mortality, affecting also quality of life (QoL), thus representing an important public health concern. From a clinical point of view, PAD may be initially symptomatic with intermittent claudication (IC), and in critical limb ischemia (CLI), an advanced stage of PAD, with rest pain, and also with leg skin ulceration, a complication that may even lead to limb loss for amputation. From a pathophysiological point of view, in the presence of atherosclerosis, endothelial activation and dysfunction lead to hemodynamic alterations such as turbulent flow, abnormal shear stress, loss of potential energy, anomalies of vascular tone with functional impairment during leg exercise in early stages, with IC onset, and in advanced stages, during CLI stage, also with rest pain as a result of an important demand/perfusion mismatch. Endothelial dysfunction, and vascular tone are also regulated by sex hormones, and incidence and prevalence of PAD have usually been found to be higher in men than in women, and, more in general, males have a higher risk of developing cardiovascular disease during the reproductive period in comparison with females of the same age. This sex related difference in developing the disease was hypothesized to be related to the protective role of estrogens in female subjects, and harmful effects of androgens in male individuals. Furthermore, the androgen receptor (AR) seems to have a role in neointima formation, in influencing the size and the composition of atherosclerotic plaques, and also vascular smooth muscle cells (VSMCs) activity. Moreover, sex-specific effects on the metabolic system are well-known and associated with different risk profiles for cardiovascular disease and they have been also related to differences in sex hormones activities. In fact, the insulin and IGF-I signaling is mediated by hormone interaction with the insulin receptor (IR) and the IGF-I receptor (IGF-IR) which are members of subclass II of the tyrosine kinase receptor super-family and they, on one hand, participate to the metabolic homeostasis, and on the other hand, they have a direct role on VMMCs, and also in some stages of the atherosclerotic process..

The aim of this study is to evaluate the role of AR, IGF-IR, and IR on the arterial wall of male patients with PAD undergoing open revascularization surgery.