טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentTsimerman Gala
SubjectMicroparticles Involvement in Vascular Complications in
Diabetes
DepartmentDepartment of Medicine
Supervisors Professor Ariel Roguin
Assistant Professor Anat Aharon
Full Thesis textFull thesis text - English Version


Abstract

Diabetes Mellitus (DM) is a common metabolic disease world-wide. DM is associated with endothelial damage and low-grade inflammatory process which is tightly linked to endothelial dysfunction. DM also presents an elevation in thrombogenic state that occurs due to alterations in coagulation factors, such as tissue factor (TF). TF is the primary physiological initiator of blood coagulation and is present in normal blood vessels and atherosclerotic plaques. In addition, there is a circulating pool of thrombogenic TF in the blood that is associated with microparticles (MPs). MPs are released from cell membrane of various cell types following apoptosis or cell activation. MPs are associated with thrombosis, inflammation and angiogenesis processes, therefore may be involved in the development of diabetic vascular complications (DVC).

            The study aim was to characterize MPs derived from DVC, including: coronary artery disease (D+C), diabetic retinopathy (DR) and two severities of diabetic foot (F2 and F3) compared to healthy controls (HC). Additional goal was to examine their thrombogenic and angiogenic effects on human umbilical cord vein endothelial cells (HUVEC).

      DVC-MPs differ in characteristics and in their thrombogenic and angiogenic effects on HUVEC. DVC patients presented up to 3.5 fold increase of Annexin V positive MPs and MPs originated from platelets, compared to HC. There were no changes in coagulation factors expression of DR-MPs compared to HC-MPs however, the MPs from the remaining DVC groups exhibited higher thrombogenicity. MPs from DR and F3 demonstrated an increased angiogenic phenotype compared to HC. HUVEC exposed to DVC-MPs demonstrated up to 5 fold increase in TF antigen and mRNA expression compared to cells stimulated by MPs from HC. Furthermore, MPs from DR caused HUVEC to create branched but unstable networks, while HUVEC stimulated by MPs from F3 created branched and stable networks, nevertheless, included apoptotic cell clusters.

We conclude that MPs from DVC reflect the physiologic state and affect the balance of thrombogenic, angiogenic and Inflammatory factors. Our findings may clarify the role of MPs in DVC pathologies.