Notch1 regulates angiogenesis in a cardiac hypertrophy model by mediating VEGF and PDGF-BB
WANG Ruixuan
BA Lina
WU Nan
Abstract：Objective To investigate the role and mechanism of Notch1 in regulating angiogenesis in a cardiac hypertrophy model.Methods The transverse aortic constriction(TAC)was performed to establish a mouse model of cardiac hypertrophy,and angiotensin Ⅱ(Ang Ⅱ)induction was performed to create a human coronary artery endothelial cell(HCAEC)injury model.Cardiac function was assessed by echocardiography,and the cardiac hypertrophy model was validated by morphological observation of the heart.The effect of Ang Ⅱ on endothelial cell viability was detected by MTT assay.The protein expressions of Notch1,vascular endothelial growth factor(VEGF),and platelet-derived growth factor-BB(PDGF-BB)were detected by Western blot.Endothelial cell migration was evaluated by the scratch assay.Results Echocardiography and cardiac morphology results revealed that compared to the sham-operated rats,the left ventricular ejection fraction(LVEF)and fractional shortening(LVFS)significantly decreased in cardiac hypertrophy rats,while the heart weight/body weight ratio and heart weight/tibia length ratio significantly increased,indicating a successful construction of the cardiac hypertrophy model(P<0.05).MTT assay showed a significant decrease in the viability of Ang Ⅱ-induced HCAECs,suggesting that Ang Ⅱhad a damaging effect on HCAECs.Western blot demonstrated that in both the cardiac hypertrophy and endothelial injury models,Notch1,and angiogenesis markers VEGF and PDGF-BB were significantly downregulated(P<0.05).In vitro,Notch1,VEGF and PDGF-BB were significantly upregulated in Ang Ⅱ-induced HCAECs overexpressing Notch1 than those of Ang Ⅱ-induced HCAECs(P<0.05).Overexpression of Notch1 in Ang Ⅱ-induced HCAECs significantly increased the migration(P<0.05).Conclusion Activation of Notch1 may promote angiogenesis by affecting the protein expressions of VEGF and PDGF-BB,thereby alleviating cardiac hypertrophy.
Keywords：cardiac hypertrophyangiogenesisendothelial cellsNotch1
Publication Date：2026-02-26
Online Publishing Date：2026-03-23(First online date of this platform, not the publication date of the document)
Pages：5( 207-211 )