JVS - Vascular Science (Jan 2022)
Zinc deficiency impairs ischemia-induced angiogenesis
Abstract
Objective: Zinc is an important essential trace metal involved in many physiologic functions, and its deficiency can affect the development of multiple organs, including the vasculature. However, clarity is lacking regarding the effects of zinc deficiency in the regulation of angiogenesis. We investigated the effects of zinc deficiency on the revascularization process through animal experiments and examined the relationship between the circulating zinc levels and tissue blood perfusion in patients with chronic limb-threatening ischemia (CLTI). Methods: Zinc-deficient mice and control wild-type mice had undergone surgery to create unilateral hindlimb ischemia. Next, we examined the relationship between the serum zinc levels and skin perfusion pressure (SPP) as an index of tissue blood perfusion in patients with CLTI. A total of 51 patients with CLTI who had been referred for de novo revascularization for CLTI due to arteriosclerosis obliterans at our hospital from May 2012 to March 2016 were enrolled. Results: The zinc-deficient mice showed a significant reduction in blood flow recovery rates in the ischemic limb and capillary density in the ischemic adductor muscle fibers compared with the control wild-type mice. The zinc-deficient mice also showed increased reactive oxygen species production after hindlimb ischemia. Nicotinamide adenine dinucleotide phosphate oxidase inhibitors ameliorated the zinc deficient-induced impairment of revascularization. The serum zinc levels were positively associated with the SPP in the CLTI patients. Multivariate regression analysis also revealed that the serum zinc levels were significantly correlated with the SPP in patients with CLTI. Conclusions: Zinc deficiency impaired the rate of ischemia-induced revascularization through enhanced oxidative stress rates, suggesting that nutritional management for zinc sufficiency could be useful in CLTI prevention and treatment. : Clinical Relevance: In the present study, we investigated the effects of zinc deficiency on angiogenesis. We found that zinc deficiency impaired the rate of ischemia-induced revascularization through enhanced oxidative stress rates in animal model. In addition, the skin perfusion pressures were positively associated with the serum zinc levels in patients with chronic limb-threatening ischemia. Thus, the intake of zinc could be useful for the prevention and/or treatment of ischemic limb disease. Circulating zinc levels could be a useful marker for the assessment of atherosclerosis-based vascular disease such as limb ischemia. Possibly, nutritional improvement by zinc intake could lead to the prevention and treatment of ischemic vascular disease.
