Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway

Abstract

Background: The flowers of Carthamus tinctorius L. are widely used in traditional Chinese medicine to treat cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA), the main constituent of C. tinctorius L. flowers, is known for its multiple biological activities. The present study investigated the effects of HSYA on angiogenesis in vitro and in a mouse hindlimb ischemia model. Methods: Using human umbilical vein endothelial cells (HUVEC) in vitro and a mouse hindlimb ischemia model in vivo, the angiogenic role of HSYA was evaluated. Results: HSYA significantly increased the capillary-like tube formation and migration of HUVEC. HSYA not only induced a rise in the expression of angiopoietin 1 and Tie-2 but it also increased phosphorylation of Tie-2, Akt, and extracellular signal-regulated kinase 1/2. Furthermore, an anti-Tie-2 neutralizing antibody significantly inhibited HSYA-induced HUVEC tube formation and migration. In vivo, the recovery of perfusion of ischemic hindlimb tissue after femoral artery interruption was significantly increased in HSYA-treated mice compared to vehicle controls. Consistent with these results, the arteriole and capillary densities in ischemic gastrocnemius muscles were significantly increased in HSYA-treated mice. Conclusions: These results indicate the potential utility of HSYA for the treatment of ischemic diseases.

Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway

“…The migration and capillary-like tube formation of ECs play a key role in vascular remodeling and regeneration. 50 In this study, unexpectedly, we observed a decrease in migration of HUVECs with increasing concentrations of HANPs ( Figure 7A and B), and this trend was also observed in the experiment of tube formation ( Figure 7D and E). Our findings were in agreement with a recent study showing that HUVECs cultured on pure PLA scaffolds exhibited larger and more highly developed vascular structures compared to those on the nano-HAP-conjugated scaffolds.…”

“…As depicted in Figure 2B, HUVECs' exposure to HAPs (25,50, 100 and 200 μg/mL) did not show any significant change in necrosis. Moreover, no significant difference of apoptosis was detected when incubated with np20 and m-HAP for 24 h compared to control (P.0.05); in comparison, HUVECs exposed to 100 and 200 μg/mL np80 for 24 h showed a significant increase in apoptotic rate as compared to control ( Figure 2C).…”

Nucleolin mediated pro‐angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post‐transcriptional regulation of VEGF‐A and MMP‐9

“…Its antiangiogenic effect was firstly found on the chick embryo chorioallantoic membrane through inhibiting the mRNA expressions of bFGF, VEGF and VEGF‐F (flt‐1) 36. Lately, Chen et al12 found that HSYA promoted angiogenesis via the angiopoietin 1/tie‐2 signalling pathway using HUVECs in vitro and a mouse hindlimb ischaemia model in vivo. Wei et al 14.…”

“…What is worth to be mentioned is the pro‐angiogenic effect of HSYA which has been reported in different ischaemic models recently 12, 14. However, the underlying mechanisms have not yet been fully elucidated.…”

“…Hydroxysafflor Yellow A (HSYA), a most representative and water‐soluble ingredient of Carthamus tinctorius L., has long been used in the treatment of myocardial ischaemia in China and exhibits prominently antiplatelet, anti‐inflammatory, antioxidant and pro‐angiogenic activities 10, 11, 12, 13. What is worth to be mentioned is the pro‐angiogenic effect of HSYA which has been reported in different ischaemic models recently 12, 14.…”