Long-term therapy with the acorn cardiac support device normalizes gene expression of growth factors and gelatinases in dogs with heart failure

J Heart Lung Transplant. 2005 Oct;24(10):1619-25. doi: 10.1016/j.healun.2004.07.022.

Abstract

Background: Passive mechanical containment of the failing left ventricle with the Acorn Cardiac Support Device (CSD) was shown to prevent progressive left ventricular dilation in dogs with heart failure and increase left ventricular ejection fraction. To examine possible mechanisms for improved cardiac function with a CSD, we examined the effect of CSD therapy on the mRNA gene expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP) 2 and 9, and tissue inhibitors of metalloproteinases (TIMP) 1 and 2.

Methods: Heart failure was produced in 12 dogs by multiple sequential intracoronary microembolizations. Six dogs were implanted with the CSD and 6 served as concurrent controls. Left ventricular tissue from 6 normal dogs was used for comparison.

Results: Compared with normal dogs, dogs with untreated heart failure showed downregulation of mRNA expression for VEGF and bFGF, whereas upregulation of mRNA expression for MMP-2 and MMP-9 was observed. Normalization of mRNA expression for all these genes was seen after treatment with the CSD.

Conclusions: This study shows that preventing left ventricular dilation and myocardial stretch with the CSD promotes normalization of growth factor and MMP gene expression. These results suggest that modulation of gene activity may, in part, contribute to the improvement of left ventricular function observed with CSD therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cardiac Catheterization
  • Dilatation, Pathologic / etiology
  • Dilatation, Pathologic / therapy*
  • Disease Models, Animal
  • Disease Progression
  • Dogs
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblast Growth Factor 2 / biosynthesis
  • Gene Expression
  • Gene Expression Regulation
  • Heart Failure / complications
  • Heart Failure / therapy*
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 2 / biosynthesis
  • Prosthesis Implantation*
  • RNA, Messenger / biosynthesis
  • Sequence Analysis, DNA
  • Stroke Volume
  • Surgical Mesh*
  • Tissue Inhibitor of Metalloproteinase-1 / analysis
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / analysis
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / therapy*

Substances

  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2