Profilin-1 contributes to cardiac injury induced by advanced glycation end-products in rats

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 3×109 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.

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

“…Studies performed by Badisa et al [ 24 ] suggested that the cell types examined are more inclined to withstand greater cocaine concertation, however, the present investigation indicates cardiomyocytes are more sensitive to higher cocaine concentration exposures. This finding corroborates Wu et al [ 16 ], which demonstrated cocaine concentrations between 1–100 µM abrogate potassium channel activity which in turn alters functional regulation of cardiac cells associated with cardiac arrhythmias, a known implication of cocaine induced cardiac dysregulation [ 11 , 30 ]. SEM analysis indicated that treatments at 50 µg/mL cocaine enhanced the formation of cell periphery and surface blebbing with significant reductions in cellular outgrowths and concomitant loss of spindle-to-satellite architecture.…”

“…The present study sought to investigate the phenotypic consequence of cocaine in cardiomyocyte cell lines derived from BD1Z rat cardiac tissue. These cell lines have previously been shown to be effective in elucidating the toxic effects of drugs, along with myocyte damage and cytoskeletal rearrangements associated with ABPs [ 9 , 10 , 11 ]. Though previous studies have examined the cytotoxicity and functional implications of cocaine, they have primarily concentrated on neuronal properties involved in mechanisms of addiction, with the majority implementing serum free or reduced serum in vitro conditions, in vivo models, case, and prospective studies [ 4 , 12 , 13 , 14 , 15 ].…”

Profilin 1 and Mitochondria—Partners in the Pathogenesis of Coronary Artery Disease?

“…The rise in profilin expression was associated with an increase in Rho, RAGE and p65. Again, silencing profilin ameliorated these changes [ 57 ]. The expression of the profilin gene in ECs was up-regulated by LDL cholesterol [ 58 ].…”

Hyper-Activation of Endoplasmic Reticulum Stress PERK/Calcineurin/RyR2 Signaling Pathway is Involved in AGEs-Exacerbated Post- Myocardial Infarction Ventricular Arrhythmias

“…Before establishment of MI model, AGEs-BSA and/or anti-RAGE IgG 3 (Abcam) were administrated to animals via remaining needles implemented in tail veins. The dosages anti-RAGE antibody were selected according to previous reports [19,20]. Treatments of each group were listed in Table 1.…”