Revascularization of Ischemic Tissues With Sikvav and Neuropeptide Y (Npy)

Abstract

Angiogenesis, the process of new vessel growth, is necessary for many normal physiological and pathological processes such as tumor growth, wound healing and ischemia. We have recently examined in vitroand in vivothe ability of two potent angiogenic compounds, SIKVAV (a peptide derived from the alpha chain of laminin-1) and Neuropeptide Y (NPY) to revascularize ischemic tissue. These compounds were tested in an ex vivo capillary sprouting angiogenesis assay that uses rat aortic rings. Both NPY and SIKVAV in the presence of VEGF, stimulated the formation of long sprouts at concentrations of 1 ng NPY (0.2 pmole/L) and 100 μg SIKVAV. In comparison very little sprouting occurred in the control rings and 50 ng of VEGF alone was required to induce equivalent number of sprouts as NPY. SIKVAV and NPY were further tested in vivo in a rat hindlimb ischemic model. Both compounds (500 μg SIKVAV and 10 ng of NPY) were embedded in the rat hind limb following unilateral ligation of the femoral artery 1 cm proximal to the adductor hiatus. After two weeks control peptides show little or no revascularization of the hindlimb distal to the ligation; however, both SIKVAV and NPY demonstrated a two-fold increase in new vessels in the region proximal to the ligation. Histological sections of latex perfused hindlimb demonstrated that ligated limbs had very few latex-filled dermal capillaries. Limbs treated with SIKVAV and NPY, however, demonstrated normal distribution in the dermal capillary beds. These data indicate that both SIKVAV and NPY are potent angiogenic factors that show promising potential clinical application to the revascularization of ischemic tissue.