Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice

Kishore B.S. Pasumarthi, Hidehiro Nakajima, Hisako O. Nakajima, Mark H. Soonpaa, Loren J. Field

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

Abstract

Restriction point transit and commitment to a new round of cell division is regulated by the activity of cyclin-dependent kinase 4 and its obligate activating partners, the D-type cyclins. In this study, we examined the ability of D-type cyclins to promote cardiomyocyte cell cycle activity. Adult transgenic mice expressing cyclin D1, D2, or D3 under the regulation of the α cardiac myosin heavy chain promoter exhibited high rates of cardiomyocyte DNA synthesis under baseline conditions. Cardiac injury in mice expressing cyclin D1 or D3 resulted in cytoplasmic cyclin D accumulation, with a concomitant reduction in the level of cardiomyocyte DNA synthesis. In contrast, cardiac injury in mice expressing cyclin D2 did not alter subcellular cyclin localization. Consequently, cardiomyocyte cell cycle activity persisted in injured hearts expressing cyclin D2, ultimately resulting in infarct regression. These data suggested that modulation of D-type cyclins could be exploited to promote regenerative growth in injured hearts.

Original languageEnglish (US)
Pages (from-to)110-118
Number of pages9
JournalCirculation research
Volume96
Issue number1
DOIs
StatePublished - Jan 21 2005

Keywords

  • Cardiomyocyte proliferation
  • DNA synthesis
  • Heart regeneration

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice'. Together they form a unique fingerprint.

Cite this