Angiotensin-converting enzyme inhibitory peptide attenuates cardiac hypertrophy associated with ACE2/Ang (1–7)/MasR axis and PKCβ1 pathway

Heart failure with preserved ejection fraction (HFpEF) is typically preceded by cardiac hypertrophy. Lycium barbarum L. as functional food show the health benefits of cardiovascular diseases. Whether Lycium barbarum L. protein-derived angiotensin-converting enzyme inhibitory peptide (ACEIP) has effects on improving cardiac hypertrophy is unknown. Here, HFpEF mouse model was established by a high-fat diet and 0.5 g/L Nѡ-Nitro-L-arginine methyl ester hydrochloride (L-NAME) in drinking water. Interventricular septum thickness (IVS), left ventricular posterior wall thickness (LVPW), left ventricular diameter (LVD), ejection fraction (EF) and left ventricular mass (LV Mass) were evaluated by transthoracic echocardiography. Serum n-terminal pro-brain natriuretic peptide (NT-proBNP), Ang II, Ang (1–7) concentrations were measured by ELISA, and hypertrophy by WGA staining. We found that ACEIP significantly improved diastolic dysfunction as reflected by the increase in mitral inflow E and A wave ratio (E/A ratio) and decrease in isovolumic relaxation time (IVRT). Meanwhile, LV Mass, IVS, LVPW and LVD in systolic or diastolic period were significantly reduced by ACEIP. Furthermore, ACEIP reversed protein kinase C β1 (PKCβ1) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, which were related to ACE2/Ang (1–7)/MasR axis activation. Our findings indicated that ACEIP could be a potential nutritional approach for the intervention of HFpEF.