Defective Angiogenesis Delays Thrombus Resolution

• DOI: 10.1161/atvbaha.113.302991
• Publication Date: 2014-02-14T02:12:47Z
• Authors: Sherin Alias; Bassam Redwan; Adelheid Panzenböck; Max P. Winter; Uwe Schubert; Robert Voswinckel; Maria K. Frey; Johannes Jakowitsch; Arman Alimohammadi; Lukas Hobohm; Andreas Mangold; Helga Bergmeister; Maria Sibilia; Erwin F. Wagner; Eckhard Mayer; Walter Klepetko; Thomas J. Hölzenbein; Klaus T. Preissner; Irene M. Lang
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Time Factors; Hypertension, Pulmonary; Macrophages; Neovascularization, Physiologic; Endarterectomy; Middle Aged; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Gene Expression Regulation; Chronic Disease; Human Umbilical Vein Endothelial Cells; Animals; Humans; Female; Angiogenic Proteins; Cells, Cultured; Aged

Objective— Restoration of patency is a natural target vascular remodeling after venous thrombosis that involves endothelial cells and smooth muscle cells, as well leukocytes. Acute pulmonary emboli usually resolve <6 months. However, in some instances, thrombi transform into fibrous obstructions, resulting occlusion the deep veins, or chronic thromboembolic hypertension (CTEPH). We proposed dysregulated thrombus angiogenesis may contribute to persistence. Approach Results— Mice with an cell–specific conditional deletion growth factor receptor 2/kinase insert domain protein were used model stagnant flow closely resembling human vein thrombosis. Biochemical functional analyses performed on endarterectomy specimens from patients CTEPH, nonresolving thromboembolism. Endothelial kinase subsequent ablation vascularization delayed resolution. In accordance these findings, organized CTEPH largely devoid structures. Several vessel-specific genes, such receptor, cadherin, podoplanin, expressed at lower levels white than organizing aortic aneurysms. addition, red attenuated angiogenic response induced by factor. Conclusions— present work, we propose mechanism nonresolution demonstrating abates vessel formation, misguiding Medical conditions associated development be compromising early angiogenesis.