COMP-angiopoietin 1 Gene Transfer Enhances Cutaneous Wound Healing

INTRODUCTION

The closure of cutaneous wounds involves events such as hemorrhage, inflammation, re-epithelializa- tion, granulation tissue formation, and the late remodeling phase of tissue repair. The early and acute phases of repair involve macrophage ac­cumulation, fibroblast ingrowth, matrix deposition, and angiogenesis. These events are triggered by a complex mixture of cytokines and growth factors that are released at the site of injury.

Angiogenesis is the sprouting of new blood vessels from a pre-existing network, and this process is central to the formation of granulation tissue because the ingrowth of newly formed vessels is needed to ensure the supply of oxygen, nutrients and inflammatory cells to the regenerating tissue. Previous studies have shown that delayed wound healing such as diabetic ulcers, chronic venous ulcers, pressure ulcers, and cutaneous wounds in the aged, are associated with decreased angiogenesis and altered levels of angiogenic growth factors in­cluding vascular endothelial growth factor (VEGF) and angiopoietin (Ang). Based on these results, “therapeutic angiogenesis”, i.e. supplementation of such recombinant angiogenic growth factors as VEGF, erythropoietin, nerve growth factor, platelet- derived growth factor, fibroblast growth factor and granulocyte-machrophage colony stimulating factor, has been used both in animal models and in clinical trials for patients to enhance cutaneous wound healing. cialis professional

Ang was discovered as a ligands for the tyrosine kinase with immunoglobulin and epidermal growth factor homology (Tie) 2 that was selectively ex­pressed on the vascular endothelium. There are four definitive members of the Ang family, Ang 1, 2, 3 and 4. Although the functions of Ang and Tie have not been well established, Ang is thought to be involved in the proliferation, maturation, stabili­zation and remodeling of vessels. Therefore, Ang 1 could be one of the promising candidate growth factors for therapeutic angiogenesis.

Large-scale production of recombinant Ang 1 is hindered by the aggregation and insolubility of protein. The activity of the purified protein fre­quently varies. These difficulties are due to its unique structural characteristics. COMP-Ang 1 is a soluble, stable, and potent Ang 1 variant in which the N-terminal portion of Ang 1 is replaced with the short coiled-coil domain of cartilage oligometric matrix protein (COMP). COMP-Ang 1 is more potent than native Ang 1 in phosphorylating

Tie 2 and Akt in primary cultured endothelial cells and in angiogenesis in vivo.
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In this study, we investigated the potential be­nefits of the therapy with adeno-associated systemic COMP-Ang 1 on cutaneous wound healing. The results of the study show that systemic COMP-Ang 1 treatment enhances cutaneous wound healing in vivo by promoting angiogenesis.

Category: Main

Tags: Angiogensis, COMP-angiopoietin 1, Cutaneous wound healing