Targeting Stenosis with Nucleotide-Hydrolyzing Enzymes

Elzbieta      Kaczmarek; Katarzyna      Koziak

Abstract

Well-established evidence links extracellular nucleotides to numerous vascular pathologies, including restenosis associated with angioplasty, atherosclerosis and transplant arteriosclerosis. Through activation of purinergic P2 receptors, extracellular nucleotides contribute to the pathogenesis of occlusive vascular diseases by mediating thrombosis, and vascular smooth muscle proliferation and migration. Therefore, there is a growing interest in the enzymes that hydrolyze nucleotides for their capability to modulate nucleotide-triggered pathologies. In this review, we present the current data addressing the therapeutic potential of nucleoside triphosphate diphosphohydrolases (NTPDases) to prevent intimal hyperplasia and treat vascular intimal disease. In addition, we discuss the mechanisms by which NTPDases exert protective effects in vascular function.

Keywords: Endothelium, stenosis, NTPDase, purinergic P2 receptors, extracellular nucleotides, vascular function, transplant arteriosclerosis, mediating thrombosis, nucleotide-triggered pathologies, endovascular approaches, endothelial nitric oxide synthase, balloon angioplasty, stimulate fibroblast proliferation, adenylate cyclase activity, development of intimal thickening