Atherosclerosis remains a major cause of morbidity and mortality worldwide.Intraplaque neovascularization critically promotes atherosclerotic progression and instability.Vascular endothelial growth factor A(VEGFA)stimulates aberrant microvessel growth in plaques by inducing endothelial cell proliferation and migration.Pigment epithelium-derived factor(PEDF)potently inhibits VEGFA-dependent neovascularization.This study introduces a thermosensitive hydrogel(PFSgel)developed from poloxamer 407(F127)and sodium alginate(SA)to deliver PEDF locally to atherosclerotic lesions.The PFSgel demonstrated a suitable liquid-solid transition at body temperature(37°C),then forming a stable 3D network structure after SA gelling with the Ca2+in the physiological environment which contributed to the character of controlled release.Rheological analysis confirmed its phase transition temperature of 28.7°C and notable self-healing properties,making it ideal for dynamic vascular environments.In vitro experiments showed that PFSgel could suppress VEGFA-induced endothelial cells’proliferation and migration through modulation of CD31 and MMP-2/MMP-9 signaling.Notably,in vivo degradation test validated the controlled release pattern of PFSgel.In Apoedeficient atherosclerotic mice,ultrasound-guided PFSgel injection onto the abdominal aorta enabled gradual in situ release of encapsulated PEDF.This effectively reduced plaque burden,neovascularization,and luminal stenosis,even with exogenous VEGFA administration.Histological analyses confirmed reduced lipid deposition,plaque area,and neovascularization within plaques.Overall,this novel in situforming PEDF delivery platform enables targeted suppression of pathological neovascularization via CD31 and MMP-2/MMP-9 pathways,representing a promising approach to stabilize high-risk plaques by intervening against VEGFA-dependent neovascularization.
Yi DuanJiangtao LinJiang YueYuanyuan LiJinghan LiaoYing SunQuan WangYourong DuanZhaojun Li
