Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-12156
Salguero, G; Akin, E; Templin, C; Kotlarz, D; Doerries, C; Landmesser, U; Grote, K; Schieffer, B (2008). Renovascular hypertension by two-kidney one-clip enhances endothelial progenitor cell mobilization in a p47phox-dependent manner. Journal of Hypertension, 26(2):257-268.
- Registered users only
View at publisher
BACKGROUND: Enhanced mechanical forces, e.g. in arterial hypertension, stimulate the formation of reactive oxygen species (ROS) by the NAD(P)H oxidase. Since bone marrow derived endothelial progenitor cells (EPCs) contribute to vascular remodeling and repair, we investigated whether renovascular hypertension stimulates EPC mobilization in a NAD(P)H oxidase-dependent manner. METHODS: Renovascular hypertension was induced by two-kidney one-clip (2K1C) in C57BL/6 (WT) and in mice lacking the p47phox subunit of the NAD(P)H oxidase (p47phox-/-). RESULTS: In WT, 2K1C increased blood pressure levels by 32.4 +/- 4 mmHg, which was associated with a four-fold increase in circulating EPCs (Sca-1+;Flk-1+). In p47phox-/- mice, the increase in blood pressure was significantly reduced (15.1 +/- 1.8 mmHg, P < 0.05) and not associated with increased EPCs. Inhibitors of the renin-angiotensin system (RAS) and nonspecific vasodilators normalized blood pressure and inhibited EPC mobilization in WT mice after 2K1C. In addition, p47phox deficiency and pharmacological ROS blockage abrogated 2K1C-induced blood pressure elevation and EPC mobilization. Stromal cell derived factor (SDF)-1 and matrix metalloproteinase (MMP)-9 activity in the bone marrow, required for EPC mobilization, were modulated in WT mice after 2K1C. In contrast, no alterations in SDF-1 and MMP-9 were observed in p47phox-/- mice. Moreover, enhanced migration of Lin- bone marrow mononuclear cells was observed when stimulated with plasma from 2K1C WT mice but not when stimulated with plasma from 2K1C p47phox-/- mice. CONCLUSION: Enhanced mechanical stretch in renovascular hypertension induces EPC mobilization in a p47phox-dependent manner, involving bone marrow SDF-1 and MMP-9 which may contribute to compensatory vascular adaptation in renovascular hypertension.
4 downloads since deposited on 04 Feb 2009
0 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||04 Feb 2009 11:29|
|Last Modified:||28 Nov 2013 00:13|
|Publisher:||Lippincott Wiliams & Wilkins|
|Additional Information:||This is a non-final version of an article published in final form in Journal of Hypertension|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page