AIM To investigate the effect of secreted frizzled-related protein 5 (SFRP5) on myocardial apoptosis and myocardial fibrosis in rats with ischemic heart failure (IHF) and its mechanism.
METHODS Forty SD male rats were randomly divided into sham operation group (Sham group), model group (IHF group), SFRP5 group, and SFRP5+Wnt5a agonist group (SFRP5+Foxy-5 group), with 10 rats in each group. The cardiac function indexes of rats were measured by echocardiography, the pathological changes of rat myocardium was observed by HE staining and Masson staining, and cardiomyocyte apoptosis in rats was detected by TUNEL staining. The positive expressions of fibronectin (Fn), α-smooth muscle actin (α-SMA) and cleaved cysteine aspartate proteolytic enzyme-3 (Cleaved Caspase-3) were observed by immunohistochemistry and the expressions of SFRP5 protein and wingless-type MMTV integration site family member 5a(Wnt5a)/c-Jun N-terminal kinase (JNK) signaling pathway protein in rat myocardium were detected by Western blot.
RESULTS Compared with those in the Sham group, left ventricle end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVIDs), left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) of rats in IHF group were increased, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were decreased (P<0.05). There were obvious pathological changes in myocardial tissue, the area of myocardial fibrosis and the rate of myocardial cell apoptosis were increased and the positive expressions of Fn, α-SMA and Cleaved Caspase-3 in myocardial tissue were also increased (P<0.05). The expressions of SFRP5 protein in myocardial tissue were decreased, while the expressions of Wnt5a protein and the ratio of p-JNK/JNK were increased (P<0.05). Compared with those in the IHF group, the indexes of cardiac function and myocardial injury of rats in SFRP5 group were improved, the area of myocardial fibrosis was reduced, the rate of myocardial cell apoptosis was decreased and the positive expressions of Fn, α-SMA and Cleaved Caspase-3 in myocardial tissue were decreased (P<0.05). The expressions of SFRP5 protein in myocardial tissue were increased, while the expressions of Wnt5a protein and the ratio of p-JNK/JNK were decreased (P<0.05). Compared with those in the SFRP5 group, the heart function indexes of the SFRP5+Foxy-5 group were abnormal, the myocardial injury was aggravated, the area of myocardial fibrosis was increased, the rate of myocardial cell apoptosis was increased and the positive expressions of Fn, α- SMA and Cleaved Caspase-3 in myocardial tissue were increased (P<0.05). The expressions of Wnt5a protein and the ratio of p-JNK/JNK in myocardial tissue were also increased (P<0.05).
CONCLUSION SFRP5 ameliorates IHF in rats by inhibiting Wnt5a/JNK signaling pathway to alleviate cardiomyocyte apoptosis and myocardial fibrosis.
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