Introduction:
Vessel maturation is dependent on platelet-derived growth factor (PDGF), which signals via tyrosine kinase receptors and facilitates recruitment of pericytes to endothelial cells (ECs). Pericytes are perivascular mural cells that induce vessel maturation, endothelial barrier function, and are involved in vessel contraction and dilatation. PDGF receptor beta (PDGFR-ß) is a widely expressed pericyte marker but is also expressed in other cell types such as neural progenitors and myofibroblasts. Since the specific role of pericyte PDGFR-ß in the cardiovascular system is unknown, we assessed its role in vessel growth and stability using pericyte-specific PDGFR-ß knock out mice.

Results:
To investigate the effect of PDGFR-ß knockout in vivo, we established NG2-Cre PDGFR-ß-flox mice, in which PDGFR-ß can be specifically be deleted in pericytes by tamoxifen injection. PDGFR-ß knockout mice showed a significant reduction of retinal vessels by 23.2+/-7.1 % at day 5 after birth (P5) (p=0.003). Accordingly, the length of the angiogenic front was reduced to 88.8+/-3 % (p=0.0001; n=14 wt; n=18 PDGFR-B KO). Moreover, we observed retinal bleedings indicating leakage caused by PDGFR-ß depletion. Vessel malformations in the form of vascular ectasia were detected in 10% of the KO mice retinas at P10. Pericyte-specific PDGFR-ß KO is associated with detachment of pericytes in retinas and kidneys of the knockout mice. Preliminary data addressing the effect of PDGFR-ß in neovascularization after myocardial infarction revealed a reduced capillary density (reduction of 46.00+19.36 % ; n=4; p= 0.055) and an increase of infarct size and fibrosis as quantified by Van-Gieson staining (to 159+-12%; n=3; p=0.10) and by Collagen immunofluorescence staining (increase of 251.6+/-62.57% compared to control; p=0.006). PDGFR-ß silencing in vitro significantly decreased Angiopoetin1 and TGF-ß1 expression in pericytes. Furthermore PDGFR-B silencing modulated transdifferentation of pericytes by significant decreasing of NG2 expression but increasing aSMA and Calponin expression. 

Conclusions:
Here we established a pericyte-specific inducible PDGFR-ß knock out mouse model. The specific in vivo knockout of the PDGF receptor beta in NG2 positive pericytes leads to a reduction in angiogenesis and vessel growth in the retina model. To investigate the role of PDGFR-B KO on adverse remodeling and neovascularization, we performed AMI model which reveals less neovascularisation and increased infarct size accompanied with higher matrix deposition after AMI. In vitro studies of PDGFR-ß silencing show significant decreases in Angiopoetin1 and TGF-ß1 expression accompanied by transdifferentation of pericytes.