Shengmai Injection suppresses endoplasmic reticulum stress caused myocardial fibrosis by controlling miR-21 expression in cardiac fibroblasts

AIM To investigate the effects of Shengmai Injection in a mouse model of heart failure caused by myocardial infarction and whether it reduced fibrosis.

METHODS  Myocardial infarction model and Angiotensin II (Ang II) model were established. Echocardiography was conducted to evaluate the cardiac function and structure in mice and myocardial fibrosis was evaluated with Masson staining. RT-qPCR was used to measure the levels of miR-21, COL1A1 mRNA and COL3A1 mRNA, while Western blot was employed to measure GRP78, CHOP and caspase-12 levels in both cardiac tissue and cardiac fibroblasts (CFs).

RESULTS  Masson staining of myocardial tissue, found that Shengmai injection can effectively slow the progression of myocardial fibrosis in mice after myocardial infarction and reduce the expression of miR-21, GRP78, CHOP, and caspase-12 (P<0.05, P<0.01). Additionally, cell experiments showed that Ang II significantly promotes the proliferation of cardiac fibroblasts (CFs) and cardiac microvascular endothelial cells (CMECs) (P<0.01), and upregulates the expression of COL1A1, COL3A1, miR-21, GRP78, CHOP, and caspase-12 in CFs (P<0.01). After inhibiting miR-21, the expression levels of COL1A1, COL3A1, GRP78, CHOP, and caspase-12 in CFs significantly decreased (P<0.05); Shengmai injection can also downregulate the expression of COL1A1, COL3A1, miR-21, GRP78, CHOP, and caspase-12 (P<0.05), inhibit the proliferation of CFs, and collagen synthesis (P<0.05).

CONCLUSION  The administration of Shengmai injection effectively reduces myocardial fibrosis in mice with heart failure following a myocardial infarction by regulating miR-21 expression and diminishing reticulum stress in cardiac fibroblasts.