Effect of apelin on the cardiac hemodynamics in hypertensive rats with heart failure
Authors: Hui Pang
Bing Han
Tao Yu
Zhenkun Zong
Journal: International Journal of Molecular Medicine (2014)
Discipline: CLINICAL MEDICINE
Keywords: apelin; hypertension; heart failure; Pyr-AP13; cardiac hemodynamics

Abstract:  It is known that apelin has definite protective effects on various cardiovascular diseases; however, the mechanism through which hypertension with heart failure (H-HF) is affected by pyroglutamylated apelin-13 (Pyr-AP13) remain unclear. Thus, in the present study, we investigated the effects of apelin on the cardiac hemodynamics in rats with hypertension and heart failure. In our study, cardiac function, dimensions and histological determination of the fibrosis of rats with two-kidney, one-clip induced hypertension and sham-operated rats were assessed using an echocardiography system and Masson's trichrome. The infusion of either 5% glucose injection (GS) alone or 5% GS containing Pyr-AP13 as a dose, time-matched design on the cardiac hemodynamics in H-HF rats and sham-operated rats was recorded. For the determination of the effects of potential related proteins on cardiac hemodynamics in the H-HF rats, the animals were divided into 5 groups: i) the sham-operated group (n=8); ii) H-HF (n=8); iii) H-HF with infusion of 0.1 µg dose of Pyr-AP13 (n=8) or 5% glucose (GS) (n=8); iv) H-HF with infusion of 1 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8); and v) H-HF with infusion of 10 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8). The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) was determined by ELISA. The expression of membrane and cytosolic proteins was evaluated by western blot analysis. Significant cardiac and perivascular fibrosis was observed in the H-HF rats. Following the infusion of Pyr-AP13, the systolic and diastolic function was significantly improved in the cardiac hemodynamic parameters in the H-HF rats treated with Pyr-AP13. The apelin receptor (APJ), which was activated by the exogenous infusion of Pyr-AP13, was partially recycled from the cytoplasm back to the plasma membrane; however, membrane APJ was eventually downregulated in the H-HF rats treated with Pyr-AP13 compared with the sham-operated group rats. Our findings suggested that a complex was formed after Pyr-AP13 combined with cellular membrane APJ receptor. However, the endogenous downregulation of the APJ receptor results in benefits from the exogenous administration of apelin. 

Retracted: No

PubPeer comments:
 if you are an expert in heart biology or experiment. you can draw a conclusion that FIG5B is just the background of the heart, not the JC-1 staining result or mitochondrial u0394u03a8m. JC-1 is only suited for use on live samples . ![file] Analysis of mitochondrial membrane potential (u0394u03a8m) u0394u03a8m was measured using the sensitive fluorescent probe JC-1, a cationic dye of 5,5u2032,6,6u2032-tetrachloro1,1u2032,3,3u2032-tetraethyl benzimidazol carbocyanine iodide (T3168, Invitrogen). Briefly, stained mouse **frozen heart slides **with 2.5 mg mL JC-1 (100 u03bcl) at room temperature for 20 min in a darkness place. The stained slides were washed three times with PBS and then analyzed immediately with the LSM-710 confocal microscope (Zeiss). For each slide, 4 different fields were selected randomly to acquire images and the average intensity of red and green fluorescence was determined. , 
 I am very curious why the background of Fig5D are different? , 
 FIG1E ![file] FIG2B ![file] FIG3J ![file] FIG4J ![file] SO vascular fibrosis=myocardial fibrosisuff1fuff1fuff1fuff1fWhy did the author use the results of vascular myocardial fibrosis instead of myocardial fibrosis? ,