The role of endothelial progenitor cells in arterial and venous thrombosis and vascular remodeling in atherosclerotic mice

Author(s)

Micheli Severo Sielski

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2015-06-08

Examining board members

Cristina Pontes Vicente; Joyce Maria Annichino Bizzacchi; Nicola Amanda Conran Zorzetto

• Advisor: Cristina Pontes Vicente

Abstract

Venous and arterial thrombosis are considered the leading cause of death the world nowdays. One of the main health complications is that arterial thrombosis may facilitate the occurrence of stroke and myocardial infarction, and also venous thrombosis may lead to pulmonary embolism. Endothelial progenitor cells (EPC) were described in 1997 by Asahara et al., and are present in peripheral blood and bone marrow. These cells present characteristics of pluripotent imature cells that can proliferate, migrate and differentiate into mature endothelial cells, and are able to migrate to the lesion site helping in vascular repair. The objective of this work was to verify the influence of EPC, used as cellular therapy in arterial and venous thrombosis and neointimal formation in atherosclerotic mice. In these work, we used LDL receptor deficient mice. These mice when fed with high fat diet present elevated cholesterol levels and are prone to develop artheroma plaques in the vessel wall. We also isolated mononuclear cells from femur and tibia using ficoll gradient and differentiated them in to EPC with EGM-2 medium until the 5th passage. Arterial and venous thrombosis were induced using Ferric chloride and thrombosis time was determined using an ultrasound probe. The treatment using EPCs was made using two injections, 10 min and 24 hours after lesion. No injection were done in control animals. After thrombosis induction the animals were euthanized immediately, 3, 7 or 14 days after lesion. while in venous thrombosis the animals were euthanized at time zero, 3 or 7 days after lesion. Lesioned vessels were collected and histologically analyzed. We were able to observe that EPC injections interfere with thrombosis time, increasing it significantly in both arterial and venous thrombosis. EPC injection also decreased neointimal formation in both vessels. After 14 days of lesion, we also observed an increase in gelatinases activity in lesioned arteries, but the same increase was not observed in lesioned veins. We conclude that EPC when used as a treatment can reach the lesioned site altering thrombosis time and thrombus matrix remodeling promoting vascular repair (AU)

• FAPESP's process: 13/10942-3 - The role of endothelial progenitor cells in arterial and venous thrombosis and vascular remodeling in atherosclerotic mice
• Grantee: Micheli Severo Sielski
• Support Opportunities: Scholarships in Brazil - Master