Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting TGF-β1/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure

Cell Physiol Biochem. 2016;39(1):294-302. doi: 10.1159/000445624. Epub 2016 Jun 27.

Abstract

Backgroun/Aims: To explore the effect of cardiac contractility modulation (CCM) on myocardial fibrosis in heart failure and to investigate the underlying mechanism.

Methods: Rabbits were randomly divided into sham group, HF group and CCM group. A rabbit model of chronic heart failure (CHF) was induced 12 weeks after aortic constriction by pressure unloading. Then cardiac contractility modulation was delivered to the myocardium lasting six hours per day for 4 weeks. Histology examination was carried out to evaluate the myocardial pathological changes. Protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-β1 and Smad3 were measured by western blot analysis.

Results: Histology examination results showed that CCM therapy attenuated myocardial fibrosis and collagen deposition in rabbits with CHF. In addition, protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-β1 and Smad3 were down regulated.

Conclusion: CCM therapy exerted protective effects against myocardial fibrosis potentially by inhibiting TGF-β1/Smad3 signaling pathway in CHF rabbits.

MeSH terms

  • Actins / metabolism
  • Animals
  • Aorta / pathology
  • Blotting, Western
  • Chronic Disease
  • Collagen / metabolism
  • Constriction, Pathologic / complications
  • Disease Models, Animal
  • Electric Stimulation Therapy / methods*
  • Female
  • Fibrosis / therapy
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Muscle, Smooth / chemistry
  • Myocardial Contraction*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Rabbits
  • Random Allocation
  • Signal Transduction*
  • Smad3 Protein / metabolism*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Actins
  • Smad3 Protein
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • Collagen
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9