Abstract
Smooth muscle cell (SMC) migration occurs in many arterial diseases, including aneurysm, angioplasty restenosis and atherosclerosis. Eph receptor
tyrosine kinases and ephrin ligands signalling, play an important role in
SMC migration. It has been reported that expression of one member of
Eph family, EphB2 receptor, is upregulated in injured vessels. To get more
insight into the regulation of vascular integrity by EphB2 in pathological
contexts, we interbred Ephb2-/- mice with atherosclerosis-prone Apoe-/-
mice and thereby generated Ephb2-/- Apoe-/- offspring. Animals were fed
a normal diet and analysed at the age of 25 weeks. We detected a 40%
increase in lipid staining in Ephb2-/- Apoe-/- thoracic aortas relative to
controls (6.58±2.5% and 3.9±1.1%, respectively; n = 5). Atherosclerotic
plaques of Ephb2-/- Apoe-/- mice exhibit a marked thinning of the
tunica media. Loss of medial smooth muscle cells and elastic fibres was
observed without any significant increase in intimal macrophage content.
Interestingly, we detected the formation of saccular aneurysms in high
haemodynamic stress regions within the arterial tree, such as aortic root and
collateral arteries of the abdominal aorta. These aneurysms are composed
of only intima and adventitia. Transgenic mice expressing a fusion protein,
in which kinase domain of EphB2 have been replaced by beta-galactosidase
(βGal), showed similar saccular aneurysms in Apoe-/- genetic background,
suggesting that EphB2 kinase activity is indispensable in this setting.
Ephb2-βGal staining is enhanced in atherosclerotic plaques and aneurysms.
In conclusion, Ephb2 receptor regulation could play a pivotal role in the
maintenance of vascular integrity in atherosclerosis.
tyrosine kinases and ephrin ligands signalling, play an important role in
SMC migration. It has been reported that expression of one member of
Eph family, EphB2 receptor, is upregulated in injured vessels. To get more
insight into the regulation of vascular integrity by EphB2 in pathological
contexts, we interbred Ephb2-/- mice with atherosclerosis-prone Apoe-/-
mice and thereby generated Ephb2-/- Apoe-/- offspring. Animals were fed
a normal diet and analysed at the age of 25 weeks. We detected a 40%
increase in lipid staining in Ephb2-/- Apoe-/- thoracic aortas relative to
controls (6.58±2.5% and 3.9±1.1%, respectively; n = 5). Atherosclerotic
plaques of Ephb2-/- Apoe-/- mice exhibit a marked thinning of the
tunica media. Loss of medial smooth muscle cells and elastic fibres was
observed without any significant increase in intimal macrophage content.
Interestingly, we detected the formation of saccular aneurysms in high
haemodynamic stress regions within the arterial tree, such as aortic root and
collateral arteries of the abdominal aorta. These aneurysms are composed
of only intima and adventitia. Transgenic mice expressing a fusion protein,
in which kinase domain of EphB2 have been replaced by beta-galactosidase
(βGal), showed similar saccular aneurysms in Apoe-/- genetic background,
suggesting that EphB2 kinase activity is indispensable in this setting.
Ephb2-βGal staining is enhanced in atherosclerotic plaques and aneurysms.
In conclusion, Ephb2 receptor regulation could play a pivotal role in the
maintenance of vascular integrity in atherosclerosis.
| Original language | Undefined/Unknown |
|---|---|
| DOIs | |
| Publication status | Published - May 2008 |
| Externally published | Yes |
| Event | 77th Congress of the European Atherosclerosis Society - Istanbul, Turkey Duration: 26 Apr 2008 → 29 Apr 2008 |
Conference
| Conference | 77th Congress of the European Atherosclerosis Society |
|---|---|
| Country/Territory | Turkey |
| City | Istanbul |
| Period | 26/04/08 → 29/04/08 |