[Loss of Myeloid-Derived Growth Factor Leads to Increased Fibrosis in Mice After Myocardial Infarction].

OBJECTIVE

To investigate the effect of the loss of myeloid-derived growth factor (Mydgf) on the transformation of cardiac fibroblasts into myofibroblasts after myocardial infarction (MI).

METHODS

Two adult mouse groups, including a wild-type (WT) group and another group with knockout (-KO), were examined in the study. The mice in these two groups were tested for their cardiac function by measuring left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (=10). Quantitative real-time PCR (qRT-PCR) (=3) was performed to determine the mRNA expression levels of myofibroblast markers, including α-smooth muscle actin (), periostin (), type Ⅷ collagen (), and connective tissue growth factor (). Western blot (=3) was performed to verify the protein expression levels of α-SMA. MI modeling was performed on the WT and the -KO mice. Postoperative LVEF and LVFS (=10) were then measured. The hearts were harvested and Masson staining was performed to determine the infarcted area (=10). The heart samples of -KO and WT mice were collected at d 7 and d 14 after MI, respectively, to verify the expression of myofibroblast markers (=3).

RESULTS

Compared with WT mice, LVEF and LVFS in adult -KO mice showed no significant changes (all P>0.05). However, the mRNA levels of and were upregulated, and α-SMA protein expression was also increased (all <0.05). After MI, compared with WT mice, LVEF and LVFS in -KO mice decreased, and the infarcted area increased significantly (all <0.05). Furthermore, mRNA levels of , , , and were increased in -KO mice. In addition, the α-SMA protein expression level was upregulated and α-SMA-positive fibroblasts were increased (<0.05).

CONCLUSION

Mydgf deletion promotes the transformation of cardiac fibroblasts into myofibroblasts and aggravates myocardial fibrosis after MI.