Elastin overexpression by cell-based gene therapy preserves matrix and prevents cardiac dilation

Shu Hong Li, Zhuo Sun, Lily Guo, Mihan Han, Michael F.G. Wood, Nirmalya Ghosh, I. Alex Vitkin, Richard D. Weisel, Ren Ke Li

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re-establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full-length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs). In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity (by birefringence of polarized light; P < 0.05 versus controls). As a result, infarct scar thickness and diastolic compliance were maintained and infarct expansion was prevented (P < 0.05 versus controls). Over a 9-week period, rats implanted with BMSCs demonstrated better cardiac function than medium controls; however, rats receiving BMSCs overexpressing elastin showed the greatest functional improvement (P < 0.01). Overexpression of elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell-based gene therapy provides a new approach to cardiac regeneration.

Original languageEnglish (US)
Pages (from-to)2429-2439
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Issue number10
StatePublished - Oct 2012
Externally publishedYes


  • Bone marrow stromal cells
  • Cell-based gene therapy
  • Elastin
  • Extracellular matrix
  • Heart failure

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology


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