Oxidized low density lipoprotein impairs endothelial progenitor cell function by downregulation of E-selectin and integrin alpha(v)beta5

Di Santo, S; Diehm, N; Ortmann, J; Volzmann, J; Yang, Z; Keo, H.H.; Baumgartner, I; Kalka, C (2008). Oxidized low density lipoprotein impairs endothelial progenitor cell function by downregulation of E-selectin and integrin alpha(v)beta5. Biochemical and biophysical research communications, 373(4), pp. 528-32. Orlando, Fla.: Academic Press 10.1016/j.bbrc.2008.06.066

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BACKGROUND: Oxidized low density lipoprotein (oxLDL) has been shown to induce apoptosis and senescence of endothelial progenitor cells (EPC). In the present study, we hypothesized that even sub-apoptotic concentrations of oxLDL impair the angiogenic potential of EPC and investigated if this effect is mediated by affecting adhesion and incorporation. METHODS: A co-culture system of human microvascular endothelial cells and EPC was used to study the effect of sub-apoptotic concentrations of native (nLDL) and oxLDL on cell-cell interaction. The expression and the functional role of angiogenic adhesion molecules and integrins was monitored by FACS and neutralizing assay, respectively. RESULTS: We observed an inhibition of tube formation and impairment of EPC integration into the vascular network of mature endothelial cells by oxLDL. In contrast, nLDL did not affect angiogenic properties of EPC. Incubation of EPC with sub-apoptotic oxLDL concentrations significantly decreased E-selectin and integrin alpha(v)beta(5) expression (37.6% positive events vs. 71.5% and 24.3% vs. 49.9% compared to control culture media without oxLDL). Interestingly, expression of alpha(v)beta(3), VE-cadherin and CD31 remained unchanged. Blocking of E-selectin and integrin alpha(v)beta(5) by neutralizing antibody effectively inhibited adhesion of EPC to differentiated endothelial cells (56.5% and 41.9% of control; p<0.001). CONCLUSION: In conclusion, oxidative alteration of LDL impairs angiogenic properties of EPC at sub-apoptotic levels by downregulation of E-selectin and integrin alpha(v)beta(5), both substantial mediators of EPC-endothelial cell interaction.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology

UniBE Contributor:

Di Santo, Stefano; Diehm, Nicolas Alexander; Ortmann, Jana; Yang, Zijiang; Keo, Hak Hong; Baumgartner, Iris and Kalka, Christoph

ISSN:

0006-291X

ISBN:

528-32

Publisher:

Academic Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:02

Last Modified:

04 May 2014 23:18

Publisher DOI:

10.1016/j.bbrc.2008.06.066

Web of Science ID:

000258208500014

URI:

https://boris.unibe.ch/id/eprint/26865 (FactScience: 91589)

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