Abstract
Cardiac injury, including hypertrophy and fibrosis, induced by advanced glycation end products (AGEs) has an important function in the onset and development of diabetic cardiomyopathy. Profilin‑1, a ubiquitously expressed and multifunctional actin‑binding protein, has been reported to be an important mediator in cardiac hypertrophy and fibrosis. However, whether profilin‑1 is involved in AGE‑induced cardiac hypertrophy and fibrosis remains to be determined. Therefore, the present study aimed to investigate the function of profilin‑1 in cardiac injury induced by AGEs. The model of cardiac injury was established by chronic tail vein injection of AGEs (50 mg/kg/day for 8 weeks) in Sprague‑Dawley rats. Rats were randomly assigned to control, AGEs, AGEs + profilin‑1 shRNA adenovirus vectors (AGEs + S)or AGEs + control adenovirus vectors (AGEs + V) groups. Profilin‑1 shRNA adenovirus vectors were injected via the tail vein to knockdown profilin‑1 expression at a dose of 3x109 plaque forming units every 4 weeks. Echocardiography was performed to measure cardiac contractile function. Cardiac tissues were stained with Masson's trichrome stain to evaluate ventricular remodeling. The serum levels of procollagen type III N‑terminal peptide were detected by ELISA. The expression of profilin‑1, receptor for AGEs (RAGE), Rho, p65, atrial natriuretic peptide, β‑myosin heavy chain, matrix metalloproteinase (MMP)‑2 and MMP‑9 were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and/or western blot analysis and immunohistochemistry staining. The results demonstrated that chronic injection of exogenous AGEs led to cardiac dysfunction, hypertrophy and fibrosis, as determined by echocardiography, Masson trichrome staining and the expression of associated genes. The expression of profilin‑1 was markedly increased in heart tissue at the mRNA and protein level following AGE administration, as determined by RT‑qPCR and western blotting, which was further confirmed by immunohistochemistry staining. Furthermore, the expression of RAGE, Rho and p65 was also increased at the protein level. Notably, knockdown of profilin‑1 expression ameliorated AGE‑induced cardiac injury and reduced the expression of RAGE, Rho and p65. These results indicate an important role for profilin‑1 in AGE‑induced cardiac injury, which may provide a novel therapeutic target for patients with diabetic heart failure.