**1. Introduction**

Peripheral artery disease (PAD) is one of the common vascular complications in diabetes mellitus [1]. Patients with PAD exhibit poor lower extremity function and develop critical limb ischemia and ulceration, ultimately leading to limb amputation [2–4]. Moreover, compared to healthy individuals, diabetic patients with PAD exhibit cardiovascular co-morbidities, neuropathy, and higher mortality [5–8]. Patients with PAD show poorer outcomes after leg bypass surgery with higher incidence of restenosis, longer hospitalization, and reduced amputation-free survival [8–11].

Arteriogenesis, which is an endothelial dependent process [12], is characterized by outward remodeling of pre-existing anastomoses in conducting arteries, and through this process, the blood flow to peripheral tissues can largely be restored. The process of collateral artery growth is strongly dependent on perivascular recruitment and accumulation of leukocytes, particularly macrophages, which supply growth factors and cytokines to the growing vessel [13]. In addition, lymphocytes accumulate in the perivascular space [14]; however, little is known about their function. It is well established that the presence of DM limits the process of arteriogenesis [15]. Indeed, it has been previously shown by van Weel et al. [16] that reperfusion recovery after femoral artery ligation (FAL) was significantly reduced in streptozotocin (STZ)-induced diabetic mice, as shown by laser Doppler perfusion measurements. The exact mechanisms through which impairment of arteriogenesis in DM occurs are not clear. Elevated vasomotor function attenuating the sensing of shear stress and defects in downstream monocyte signaling are reported as major contributors to the vascular impairments seen in arteriogenesis [17].

Early growth response-1 (*Egr-1*) is a zinc finger transcription factor, which is expressed after exposure of cells to mediators associated with growth and di fferentiation [18]. Several studies have shown a link between the activation of *Egr-1* through hypoxia, ischemia/reperfusion, mechanical stress, shear stress, emphysema, atherosclerosis, and acute vascular injury [19]. Early growth response-1 has been reported to play a critical role in a hind limb ischemia model [20], and in a separate study, it was shown that adenoviral-mediated *Egr-1* delivery improved perfusion recovery [21]. Early growth response-1 is important for leukocyte recruitment and vascular cell proliferation during arteriogenesis in vivo in mice subjected to FAL [22]. Thus, with increased *Egr-1* expression playing a critical role in both arteriogenesis and regulation under hyperglycemic conditions, the present study was performed to understand the influence of DM on *Egr-1* expression and its consequent biological events. We hypothesized that *Egr-1* expression may be compromised in DM which may lead to impaired collateral vessel growth. In the present study, we investigated the role of *Egr-1* in collateral artery growth in vivo in streptozotocin-induced diabetic mice employing a hind limb model in which arteriogenesis was induced by FAL.
