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Vascular Surgery 2019
Journal of Vascular and Endovascular Therapy
ISSN: 2573-4482
Page 33
March 28-29, 2019
Rome, Italy
Vascular Surgery
4
th
Edition of World Congress & Exhibition on
CD95-ligand contributes to abdominal aortic aneurysm
progression by modulating inflammation
Wanfen Xiong
University of Nebraska Medical Center, USA
Wanfen Xiong, J Vasc Endovasc Therapy 2019, Volume 4
DOI: 10.21767/2573-4482-C1-005
Statement of the Problem:
Abdominal aortic aneurysm
(AAA) is one of a number of diseases associated with a
prominent inflammatory cell infiltration, matrix protein
degradation, and smooth muscle cell apoptosis. CD95 is
an inflammatory mediator and an apoptosis inducer. How
the CD95L/CD95 contributes to aneurysm degeneration
remains largely unknown.
Methods & Results:
By using the CaCl2 murine model of
AAA, we found that both mRNA and protein levels of CD95L
were increased in aneurysm tissue compared with NaCl-
treated normal aortic tissue. To determine whether CD95L
contributes directly to aneurysm formation, we used CD95L
null (CD95L-/-) mice to examine their response to CaCl2
aneurysminduction.Sixweeksafterperiaorticapplicationof
CaCl2, aortic diameters of CD95L-/- mice were significantly
smaller compared to CaCl2-treated wild type controls.
Connective tissue staining of aortic sections from CaCl2-
treated CD95L-/- mice showed minimal damage of medial
elastic lamellae which was indistinguishable from the
NaCl-treated sham control. Furthermore, CD95L deficiency
attenuates macrophage and T cell infiltration into the aortic
tissue. To study the role of CD95L in the myelogeous cells
in AAA formation, we created chimeric mice by infusing
CD95L-/- bone marrow into sub-lethally irradiated wild
type mice (WT/CD95L-/-BM). WT/CD95L-/-BM mice
were resistant to aneurysm formation. Inflammatory cell
infiltration was blocked by the deletion of CD95L onmyeloid
cells. The levels of caspase 8 in the aortas of CaCl2-treated
wild type mice were increased compared to NaCl-treated
controls. CD95L deletion inhibited caspase 8 expression.
Furthermore, a caspase 8-specific inhibitor was able to
partially block aneurysm development in CaCl2-treated
aneurysmmodels.
Conclusion & Significance:
These studies demonstrated
that inflammatory cell infiltration during AAA formation is
dependent on CD95L from myelogeous cells. Aneurysm
inhibition by deletion of CD95L is mediated in part by down-
regulation of caspase 8.