Background:Angiotensin Ⅱ (Ang Ⅱ) is a major contributor to the development of heart failure.However,the molecular and cellular mechanisms that underlie this process remain elusive.Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction,and our previous study showed that Ang Ⅱ significantly impaired the angiogenesis response.The current study was designed to examine the role of Jaggedl-Notch signaling in the effect of Ang Ⅱ during impaired angiogenesis and cardiac hypertrophy.Methods:Ang Ⅱ was subcutaneously infused into 8-week-old male C57BL/6 mice at a dose of 200 ng·kg 1·min-1 for 2 weeks using Alzet micro-osmotic pumps.N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT),a γ-secretase inhibitor,was injected subcutaneously during Ang Ⅱ infusion at a dose of 10.0 mg·kg-1·d-L Forty mice were divided into four groups (n =10 per group):control group;Ang Ⅱ group,treated with Ang Ⅱ;DAPT group,treated with DAPT;and Ang Ⅱ + DAPT group,treated with both Ang Ⅱ and DAPT.At the end of experiments,myocardial (left ventricle [LV]) tissue from each experimental group was evaluated using immunohistochemistry,West blotting,and real-time polymerase chain reaction.Data were analyzed using one-way analysis of variance test followed by the least significant difference method or independent samples t-test.Results:Ang Ⅱ treatment significantly induced cardiac hypertrophy and impaired the angiogenesis response compared to controls,as shown by hematoxylin and eosin (HE) staining and immunohistochemistry for CD31,a vascular marker (P ＜ 0.05 for both).Meanwhile,Jaggedl protein was significantly increased,but gene expression for both Jag1 and Hey1 was decreased in the LV following Ang Ⅱ treatment,compared to that in controls (relative ratio for Jag1 gene:0.45 ± 0.13 vs.0.84 ± 0.15;relative ratio for Hey1 gene:0.51 ±0.08 vs.0.91 ± 0.09;P ＜ 0.05).All these cellular and molecular effects induced by Ang Ⅱ in the hearts of mice were reduced by DAPT treatment.Interestingly,Ang Ⅱ stimulated Hey1,a known Notch target,but did not affect the expression of Hey2,another Notch target gene.Conclusions:A Jagged 1-Hey 1 signal might mediate the impairment of angiogenesis induced by Ang Ⅱ during cardiac hypertrophy.