Arteriosclerosis, thrombosis, and vascular biology, 2018-05, Vol.38 (5), p.1076
2018
Details
- Autor(en) / Beteiligte
- Titel
- CD40L Deficiency Protects Against Aneurysm Formation
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2018-05, Vol.38 (5), p.1076
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The mechanisms underlying formation of arterial aneurysms remain incompletely understood. Because inflammation is a common feature during the progressive degeneration of the aortic wall, we studied the role of the costimulatory molecule CD40L, a major driver of inflammation, in aneurysm formation. Transcriptomics data obtained from human abdominal aortic aneurysms and normal aortas revealed increased abundance of both CD40L and CD40 in media of thrombus-free and thrombus-covered human abdominal aortic aneurysms samples. To further unravel the role of CD40L in aneurysm formation, apolipoprotein E-deficient ( ) and mice were infused with angiotensin II for 7 and 28 days. Only a minority of mice (33% and 17%) developed (dissecting) aneurysms compared with 75% and 67% of littermates after 7 and 28 days of infusion, respectively. Total vessel area of the aorta at the suprarenal level was 52% smaller in angiotensin II-infused mice compared with that in angiotensin II-infused mice. Chimeric mice repopulated with bone marrow afforded a similar protection against dissecting aneurysm formation. Moreover, lack of CD40L protected mice from fatal aneurysm rupture. T helper cell and macrophage accumulation in aneurysmal tissue was reduced in mice with a concomitant decrease in expression of proinflammatory chemo- and cytokines. In addition, aneurysms of mice displayed reduced abundance of matrix metalloproteinase-13 and an increase in tissue inhibitor of metalloproteinase-3 while activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 was diminished. Deficiency of (hematopoietic) CD40L protects against dissecting aneurysm formation and reduces the incidence of fatal rupture. This is associated with a decreased accumulation and activation of inflammatory cells and a dampened protease activity in the arterial wall.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1524-4636DOI: 10.1161/ATVBAHA.117.310640Titel-ID: cdi_pubmed_primary_29519940
- Format
- –
- Schlagworte
- Aneurysm, Dissecting - chemically induced, Aneurysm, Dissecting - genetics, Aneurysm, Dissecting - metabolism, Aneurysm, Dissecting - prevention & control, Angiotensin II, Animals, Aorta, Abdominal - metabolism, Aorta, Abdominal - pathology, Aortic Aneurysm, Abdominal - chemically induced, Aortic Aneurysm, Abdominal - genetics, Aortic Aneurysm, Abdominal - metabolism, Aortic Aneurysm, Abdominal - prevention & control, Aortic Rupture - chemically induced, Aortic Rupture - genetics, Aortic Rupture - metabolism, Aortic Rupture - prevention & control, CD40 Ligand - deficiency, CD40 Ligand - genetics, Chemokines - genetics, Chemokines - metabolism, Cytokines - genetics, Cytokines - metabolism, Dilatation, Pathologic, Disease Models, Animal, Humans, Male, Matrix Metalloproteinase 13 - genetics, Matrix Metalloproteinase 13 - metabolism, Matrix Metalloproteinase 2 - genetics, Matrix Metalloproteinase 2 - metabolism, Matrix Metalloproteinase 9 - genetics, Matrix Metalloproteinase 9 - metabolism, Mice, Inbred C57BL, Mice, Knockout, ApoE, Tissue Inhibitor of Metalloproteinase-3 - genetics, Tissue Inhibitor of Metalloproteinase-3 - metabolism