TY  - JOUR
A1  - Lautz, Thomas
A1  - Lasch, Manuel
A1  - Borgolte, Julia
A1  - Troidl, Kerstin
A1  - Pagel, Judith-Irina Carola
A1  - Caballero-Martinez, Amelia
A1  - Kleinert, Eike Christian
A1  - Walzog, Barbara
A1  - Deindl, Elisabeth
T1  - Midkine controls arteriogenesis by regulating the bioavailability of vascular endothelial growth factor A and the expression of nitric oxide synthase 1 and 3
T2  - EBioMedicine
N2  - Midkine is a pleiotropic factor, which is involved in angiogenesis. However, its mode of action in this process is still ill defined. The function of midkine in arteriogenesis, the growth of natural bypasses from pre-existing collateral arteries, compensating for the loss of an occluded artery has never been investigated. Arteriogenesis is an inflammatory process, which relies on the proliferation of endothelial cells and smooth muscle cells. We show that midkine deficiency strikingly interferes with the proliferation of endothelial cells in arteriogenesis, thereby interfering with the process of collateral artery growth. We identified midkine to be responsible for increased plasma levels of vascular endothelial growth factor A (VEGFA), necessary and sufficient to promote endothelial cell proliferation in growing collaterals. Mechanistically, we demonstrate that leukocyte domiciled midkine mediates increased plasma levels of VEGFA relevant for upregulation of endothelial nitric oxide synthase 1 and 3, necessary for proper endothelial cell proliferation, and that non-leukocyte domiciled midkine additionally improves vasodilation.
The data provided on the role of midkine in endothelial proliferation are likely to be relevant for both, the process of arteriogenesis and angiogenesis. Moreover, our data might help to estimate the therapeutic effect of clinically applied VEGFA in patients with vascular occlusive diseases.
KW  - Midkine
KW  - Arteriogenesis
KW  - Vascular endothelial growth factor A
KW  - Vascular endothelial growth factor receptor 2
KW  - Endothelial nitric oxide synthase
KW  - Neuronal nitric oxide synthase
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45608
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456087
SN  - 2352-3964
N1  - © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 27
SP  - 237
EP  - 246
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -