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 Soonpaa, Loren Field

Research output: Contribution to journalArticle

217 Citations (Scopus)

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

Fingerprint

Cyclin D2
Cyclin D
Cardiac Myocytes
Transgenic Mice
Cyclin D3
DNA
Cyclin D1
Cell Cycle
Cyclin-Dependent Kinase 4
Cardiac Myosins
Cyclins
Myosin Heavy Chains
Wounds and Injuries
Cell Division
Growth

Keywords

  • Cardiomyocyte proliferation
  • DNA synthesis
  • Heart regeneration

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice. / Pasumarthi, Kishore B S; Nakajima, Hidehiro; Nakajima, Hisako O.; Soonpaa, Mark; Field, Loren.

In: Circulation Research, Vol. 96, No. 1, 21.01.2005, p. 110-118.

Research output: Contribution to journalArticle

Pasumarthi, Kishore B S ; Nakajima, Hidehiro ; Nakajima, Hisako O. ; Soonpaa, Mark ; Field, Loren. / Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice. In: Circulation Research. 2005 ; Vol. 96, No. 1. pp. 110-118.
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