Objective To investigate whether Yiqi Fumai Lyophilized Injection [注射用益气复脉（冻干）, YQFM] ameliorates myocardial hypertrophy and pressure overload-induced heart failure (HF) by upregulating the cardiac endothelial mechanosensitive ion channel Piezo1 and activating the nitric oxide (NO) signaling pathway. Methods A mouse HF model was prepared via transverse aortic constriction (TAC) surgery. Two weeks post-operation, mice received intraperitoneal injections of different doses of YQFM (0.13, 0.26, 0.53 g/kg) or captopril (20 mg/kg) for four weeks. Cardiac function was assessed by echocardiography. Pathological injury and fibrosis were evaluated by hematoxylin and eosin (HE) and Masson staining. Cardiac remodeling and cardiomyocyte hypertrophy were assessed by heart index, heart weight-to-tibia length ratio and wheat germ agglutinin (WGA) staining. Serum biochemical assays, qRT-PCR, Western blotting and immunofluorescence were employed to detect HF-related biomarkers and the expressions of key proteins in Piezo1/NO pathway. Results YQFM significantly improved TAC-induced cardiac dysfunction and remodeling (P < 0.05, 0.01), and alleviated histopathological disorganization, cardiomyocyte hypertrophy and myocardial fibrosis (P < 0.01). Mechanistic studies showed that YQFM reduced levels of cardiac injury markers cardiac troponin T (cTn-T) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in serum (P < 0.01), and significantly downregulated the expressions of hypertrophy-related genes natriuretic peptide A (Nppa), natriuretic peptide B (Nppb), myosin heavy chain 7 (Myh7) and fibrosis-related genes collagen type I alpha 1 chain (Col1a1), collagen type III alpha 1 chain (Col3a1) in cardiac tissue (P < 0.05, 0.01). YQFM significantly decreased the levels of follistatin-like 1 (Fstl1) and endothelin-1 (ET-1) (P < 0.05, 0.01), while elevating the levels of NO in serum and cardiac tissue and cyclic guanosine monophosphate (cGMP) in cardiac tissue (P < 0.01). Furthermore, YQFM significantly upregulated the expressions of Piezo1 protein and phosphorylated endothelial nitric oxide synthase (p-eNOS) in cardiac endothelial cells (P < 0.01). Conclusion YQFM improves cardiac function and remodeling, and inhibits cardiomyocyte hypertrophy in HF by upregulating endothelial Piezo1 expression and activating eNOS/NO signaling pathway.

Yiqi Fumai Lyophilized Injection  /  heart failure  /  cardiac hypertrophy  /  transverse aortic constriction  /  Piezo1/NO/cGMP pathway