Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of
diabetes mellitus (DM), and cardiac
fibrosis is a characteristic pathological manifestation of DCM. DCM can be exacerbated by pyroptosis, and pyroptosis is a potential target of
microRNAs (
miRNAs). miR-135b is involved in delaying the progression of numerous
cardiovascular diseases, Nonetheless, the role of miR-135b in diabetic cardiac
fibrosis is unclear.
Ranolazine is a
piperazine derivative and is effective for the treatment of
cardiovascular disease. The purpose of the study was to elucidate the mechanism of action of
ranolazine against diabetic cardiac
fibrosis and to investigate the role of miR-135b in this process. Functional and structural changes in the rat heart were examined by echocardiography,
hematoxylin-
eosin (H&E) and Masson staining. Immunohistochemistry was used to assess the expression of caspase-1, interleukin-1β (IL-1β), gasdermin D (GSDMD), transforming growth factor-β1 (TGF-β1),
collagen I and
collagen III in the rat left ventricle. Western blot and immunofluorescence were used to detect the
protein expression of caspase-1, IL-1β, GSDMD, TGF-β1,
collagen I and
collagen III
proteins, and the
mRNA levels were determined using fluorescent quantitative PCR.
Ranolazine reduced pyroptosis and inhibited
collagen deposition, improving cardiac function in rats.
Ranolazine increased miR-135b expression in high
glucose-treated cardiac fibroblasts, and miR-135b directly bound to caspase-1. Interference with miR-135b reduced the effects of
ranolazine on pyroptosis and
collagen deposition.
Ranolazine treatment of diabetic cardiac
fibrosis inhibited pyroptosis and
collagen deposition by upregulating miR-135b. Our study provides a solid theoretical basis for understanding the pathogenesis of diabetic cardiac
fibrosis and the clinical use of
ranolazine in the treatment of DCM.