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Published on: March 3, 2013
CD44 regulates arteriogenesis in mice and is differentially expressed in patients with poor and good
N van Royen1, M Voskuil, I Hoefer
1Department of Cardiology, Room B2-114, Academic Medical Center, University of Amsterdam, Meibergdreef 9 1105 AZ, Amsterdam, The Netherlands. n.vanroyen@amc.uva.nl
Insights
CD44 glycoprotein is crucial for arteriogenesis, the growth of collateral arteries. Its deficiency severely impairs this process, with lower expression seen in patients with poor collateralization.
Area of Science:
- Cardiovascular Biology
- Immunology
- Molecular Biology
Background:
- Arteriogenesis, the development of collateral arteries, is orchestrated by monocytes supplying growth factors.
- CD44 glycoproteins are implicated in leukocyte extravasation and growth factor signaling.
Purpose of the Study:
- To investigate the role of CD44 in the process of arteriogenesis.
Main Methods:
- Utilized a murine hind-limb model to study arteriogenesis.
- Assessed CD44 expression and its impact on leukocyte trafficking and growth factor levels.
- Analyzed CD44 expression in monocytes from coronary artery disease patients.
Main Results:
- CD44 expression significantly increased during collateral artery growth in mice.
- Arteriogenesis was severely impaired in CD44-deficient mice, with reduced leukocyte recruitment and growth factor expression (FGF-2, PDGF-B).
- Reduced maximal CD44 expression on monocytes correlated with impaired collateral artery formation in human patients.
Conclusions:
- This study demonstrates the pivotal role of CD44 in arteriogenesis.
- CD44 deficiency significantly impedes collateral artery development.
- Lower CD44 expression on monocytes is associated with poor collateralization in patients with coronary artery disease.
Background:
Arteriogenesis refers to the development of collateral conductance arteries and is orchestrated by circulating monocytes, which invade growing collateral arteries and act as suppliers of cytokines and growth factors. CD44 glycoproteins are involved in leukocyte extravasation but also in the regulation of growth factor activation, stability, and signaling. Here, we explored the role of CD44 during arteriogenesis.
Methods And Results:
CD44 expression increases strongly during collateral artery growth in a murine hind-limb model of arteriogenesis. This CD44 expression is of great functional importance, because arteriogenesis is severely impaired in CD44-/- mice (wild-type, 54.5+/-14.9% versus CD44-/-, 24.1+/-9.2%, P<0.001). The defective arteriogenesis is accompanied by reduced leukocyte trafficking to sites of collateral artery growth (wild-type, 29+/-12% versus CD44-/-, 18+/-7% CD11b-positive cells/square, P<0.01) and reduced expression of fibroblast growth factor-2 and platelet-derived growth factor-B protein. Finally, in patients with single-vessel coronary artery disease, the maximal expression of CD44 on activated monocytes is reduced in case of impaired collateral artery formation (poor collateralization, 1764+/-572 versus good collateralization, 2817+/-1029 AU, P<0.05).
Conclusions:
For the first time, the pivotal role of CD44 during arteriogenesis is shown. The expression of CD44 increases during arteriogenesis, and the deficiency of CD44 severely impedes arteriogenesis. Maximal CD44 expression on isolated monocytes is decreased in patients with a poor collateralization compared with patients with a good collateralization.
