c-kit Is Required for Cardiomyocyte Terminal Differentiation

Li, Ming; Naqvi, Nawazish; Yahiro, Eiji; Liu, Ke; Powell, Pamela C.; Bradley, Wayne E.; Martin, David I. K.; Graham, Robert M.; Dell’Italia, Louis J.; Husain, Ahsan

doi:10.1161/circresaha.107.161737

Cited by 81 publications

(96 citation statements)

References 30 publications

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“…Bernex et al (22) and Wouters et al (23) knocked reporters into the c-kit locus, but did not examine cardiac expression, and the dominant nature of the c-kit locus complicates this strategy. A minimal c-kit promoter strategy yielded similar results with the concordance of CD117 and anti-GFP staining that declined after birth (24,25). We show that embryonic and postnatal c-kit ϩ cells are in a mixed developmental state within the developing heart (Fig.…”

Section: Discussionsupporting

confidence: 74%

“…Recent work (25) demonstrated that pressure overload results in augmented expression of c-kit in cardiomyocytes. Such expression could ref lect cardiomyogenesis from c-kit ϩ CPc, or could be the result of c-kit reexpression in committed myocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Rather, these factors indicate that c-kit reexpression occurs in differentiated cardiomyocytes at regions surrounding cardiac injury, activated by local conditions such as hypoxia or inf lammatory cytokines, because these cells are not seen at remote regions. Thus, rather than unequivocally identifying adult cardiac precursors, c-kit reexpression in adult cardiac myocytes appears to play a role in the transcriptional activation of fetal/neonatal genes that are induced during cardiac stress (25).…”

Section: Discussionmentioning

confidence: 99%

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c-kit expression identifies cardiovascular precursors in the neonatal heart

Tallini

Greene

Craven

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

198

193

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

c-kit expression identifies cardiovascular precursors in the neonatal heart

Tallini

Greene

Craven

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

198

193

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“…Although a recent report showed activation of a c-kit reporter after myocardial cryoinjury in the neonate (18), it is difficult to reach a conclusion about some minor role of progenitor cells in neonatal heart regeneration without carefully designed fate mapping studies. Although c-kit is expressed in a subset of cardiac progenitor cells, it is known that c-kit is also expressed during cardiomyocyte dedifferentiation (19,20), and proliferation (21), which are known features of the neonatal cardiac regenerative response. Therefore, future studies using detailed analysis of the extent and mechanism of regeneration in the neonatal cryoinjury model are warranted.…”

Section: Discussionmentioning

confidence: 99%

Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family

Porrello

Mahmoud

Simpson³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

660

675

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We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity.

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“…23 c-Kit is also transiently expressed in cardiomyocyte precursors during development and in a rare cell population in the normal adult heart. Li et al 24 demonstrated that in the heart, c-Kit is expressed not only by cardiac stem cells but also by cardiomyocytes. Expression is observed immediately after birth and terminates a few days later and, thus, coincides with the onset of cardiomyocyte terminal differentiation.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of statin on cardiac fibrosis and apoptosis in adrenomedullin-knockout mice treated with angiotensin II and high salt loading

et al. 2010

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Statins exert pleiotropic effects, including antioxidative and cellular protective effects. Endogenous adrenomedullin (AM) induces anti-inflammatory, anti-fibrotic and proangiogenic effects. We examined the effects of simvastatin on cardiac fibrosis and apoptosis in AM heterozygous knockout (AM +/À ) mice treated with angiotensin (Ang) II and high salt loading. Seven-weekold AM +/À mice were infused with Ang II while on a high-salt diet with or without simvastatin for 2 weeks. Hearts were stained by hematoxylin-eosin or Masson's trichrome, and were immunostained with isolectin B 4 and a-smooth muscle actin antibodies. Expression of c-Kit and Sca-1 messenger RNA (mRNA) was evaluated by real-time PCR analysis. Apoptotic cells in hearts were identified by terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL) staining. Hearts from Ang II/salt loading AM +/À mice showed marked perivascular fibrosis around coronary arteries. Treatment with simvastatin significantly inhibited the fibrosis around coronary arteries in Ang II/salt-loading AM +/À mice. Expression of c-Kit and Sca-1 mRNAs in hearts from Ang II/salt-loading AM +/À mice was significantly lower than in hearts from wild-type mice. Treatment with simvastatin significantly increased the suppressed expression of c-Kit and Sca-1 mRNAs. In addition, treatment with simvastatin significantly increased the number of isolectin B 4 -positive capillary arteries in hearts from Ang II/salt-loading AM +/À mice. Ang II/high salt significantly increased apoptotic cells in hearts from AM +/À mice; this trend was reversed by treatment with simvastatin. Thus, statins have potent cardioprotective effects that may be associated with anti-fibrotic, proangiogenic and anti-apoptotic effects in Ang II/salt-loading AM +/À mice.

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c-kit Is Required for Cardiomyocyte Terminal Differentiation

Cited by 81 publications

References 30 publications

c-kit expression identifies cardiovascular precursors in the neonatal heart

c-kit expression identifies cardiovascular precursors in the neonatal heart

Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family

Protective effects of statin on cardiac fibrosis and apoptosis in adrenomedullin-knockout mice treated with angiotensin II and high salt loading

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