At present, there are four known types of angiopoietin including ANGPT1, ANGPT2
, ANGPT3, and ANGPT4.
Malachowski et al., "VEGF, ANGPT1, ANGPT2
, and MMP-9 expression in the autologous hematopoietic stem cell transplantation and its impact on the time to engraftment," Annals of Hematology, vol.
The current concept is that FNH develops as a vascular malformation as a result of dysregulation of angiopoietin genes (ANGPT1 and ANGPT2
The Weibel-Palade bodies are specific endothelial organelles containing VWF, P-selectin (CD62P), and angiopoietin-2 (Angpt2
), participating in platelet binding, leukocyte recruitment, and modulation of inflammation, respectively .
ANGPT2 is generally considered as antagonist as it competes with ANGPT1 for binding to TIE2, reduces vessel stability, and enhances vascular remodeling .
In endothelial cells, both ANGPT1 and ANGPT2 also induce TIE2-dependent translocation of P-selectin through a PLCG1/Ca2+ signaling pathway .
Rhein affected multiple molecular targets related to angiogenesis, particularly angpt2 and tie2, and also inhibited endothelial cell migration.
So the major molecules participating in these two signaling pathways, including [VECF.sub.165], KDR, ANGPT1, ANGPT2, TIE1 and TIE2 were investigated.
In COT, hypoxia increased (P<0.03) overall mRNA expression of vascular endothelial growth factor (VEGF) by 177 [+ or -] 15%, placental growth factor (P1GF) by 195 [+ or -] 14%, angiopoietin-2 (ANGPT2
) by 180 [+ or -] 11% and ANGPT receptor Tek by 130 [+ or -] 6%, and decreased (P<0.01) expression of ANGPT1 to 79 [+ or -] 5% compared with normal [O.sub.2].
These genes include angiogenic/vascular cell growth factors (VEGF, PLGF, ADM, ANGPT2
, TGFB2), vasoactive serine proteases (KLK2, KLK6, KLK9, KLK22), and vascular endothelial receptors (IL17R, BDKRB1, ENG, GNA13).
To identify the mechanisms underpinning the increased expansion observed among HSPCs cocultured with MSCs under HP, we performed qRT-PCR to investigate the relative expression of several HSPC niche markers: ANGPT1, angiopoietin 2 (ANGPT2), jagged 1 (JAG1), osteopontin (OPN), runt-related transcription factor 2 (RUNX2), SDF1, TPO, and VCAM1.
In particular, cocultured MSCs that were subjected to HP (H_M_HP group) expressed significantly higher levels of most markers (ANGPT1, ANGPT2, JAG1, OPN, SDF1, and TPO) compared with cocultured MSCs that were not subjected to HP (H_M group).