Objectives

The main objective of WP 03 is to investigate functional and structural macrovascular effects in the irradiated arteria saphena by optical coherence tomography.

Task 1:  Study of adhesive / thrombogenic properties of irradiated endothelium
Task 2:  In vivo optical imaging of vascular function after irradiation
Task 3:  Histopathology of A. saphena

Workpackage description

• The adhesive / thrombogenic properties of irradiated endothelium will be studied at early times. Afterwards, the radiation-induced changes in inflammatory and thrombotic gene expression of atherogenic and normal mice will be investigated by qRT-PCR and immunohistochemistry for 8 markers of inflammation (P-selection, V-Cam, MCP-1, CD-40, TM, KLF2, PAI1 and vWF)
• The established method of optical coherence tomography (OCT) will be adapted to the study of perfusion and vascular tonus in the arteria saphena investigating, in parallel, left and right mouse leg. Afterwards, animals locally irradiated with 2 to 10 Gy will be investigated 3, 6, 9, and 12 months after irradiation to validate the suitability of the method for investigations of late functional changes in arteries exposed to low radiation doses to be followed by further experiments with lower radiation doses.
• Sections from fixed samples of irradiated a. saphena will be shared for histopathological evaluation of atherosclerosis and immunohistochemical analysis of thrombotic and inflammatory changes.

WP leader

Prof. Dr. Mat Daemen (CARIM) is the head of the cardiovascular research group, head of the Department of Pathology and scientific director of CARIM. Prof Daemen and his group worked for a long time on the structural and functional alterations in cardiac failure and after myocardial infarction in the rat, mouse and human heart. This work was performed in close collaboration with the Department of Pharmacology. His group was one of the first to work on the in vivo functional and structural analysis of the mouse heart and to use transgenic mouse models. For structural analysis Prof. Daemen focuses on changes in the extracellular matrix (collagen, MMP's TIMP's) and on the role of the local renin angiotensin system in the control of the extracellular matrix.

Participating consortium partners

Technische Universität München, Germany
University of Technology, Dresden; Germany
Netherland Cancer Institute, The Netherlands
University of Leipzig, Germany