Therapeutic effects of concurrent autologous bone marrow cell infusion and metabolic intervention in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb.

Abstract

Lower-limb ischemia is a major health problem especially when associated to hypercholesterolemia. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Since tissue ischemia and hypercholesterolemia are associated with an overwhelming generation of oxygen radicals, metabolic intervention with antioxidants and l-arginine can induce beneficial effects beyond those achieved by a novel therapeutic approach represented by the use of autologous bone marrow cells (BMCs). The protective effect of BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow, 0.05% vitamin C and 6% l-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb. Intravenous BMC therapy improved blood flow and increased capillary densities. This beneficial effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress and macrophage activation.