Gene therapy with CX3CL1 for murine limb ischemia

• Grant number: 16/09547-0
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2016
• Effective date (End): August 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sang Won Han
• Grantee: Carlos Alberto Vergani Junior
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia, AP.TEM

Abstract

Peripheral arterial disease (PAD) is caused by narrowing or obstruction of the arterial blood vessels. One of the main manifestations of PAD is critical limb ischemia (CLI), which is usually caused by atherosclerosis. Macrophages act in the repair of ischemic and damaged tissues or to maintain homeostasis, stimulating the formation of new vessels. Macrophages may have phenotype M1 (pro-inflammatory) or M2 (pro-resolutive). Studies show that M2 macrophages are active in angiogenesis processes, fibrosis, tissue repair and regeneration. The transmembrane protein Fractalkine/CX3CL1 is a chemotactic molecule that participates in the recruitment of monocytes LY6Clow. These monocytes are essential to pro-resolutive process of ischemic tissue because these cells acquire macrophage M2 phenotype after diapedesis. The purpose of this project is to evaluate the LY6Clow monocyte recruitment capacity by transfection of CX3CL1 gene in the ischemic limb, the formation of M2 macrophages and the ischemic muscle repair.