Heart development, diseases, and regeneration - New approaches from innervation, fibroblasts, and reprogramming

Masaki Ieda

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy.

Original languageEnglish
Pages (from-to)2081-2088
Number of pages8
JournalCirculation Journal
Volume80
Issue number10
DOIs
Publication statusPublished - 2016

Fingerprint

Cardiac Myocytes
Regeneration
Heart Diseases
Fibroblasts
Embryonic Development
Paracrine Communication
Developmental Biology
Cardiomegaly
Myocardial Ischemia
Cardiac Arrhythmias
Fibrosis
Heart Failure
Myocardial Infarction
Parturition
Mortality
Wounds and Injuries
Growth
Therapeutics

Keywords

  • Cardiac fibroblast
  • Development
  • Direct reprogramming
  • Nervous system
  • Regeneration

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Heart development, diseases, and regeneration - New approaches from innervation, fibroblasts, and reprogramming. / Ieda, Masaki.

In: Circulation Journal, Vol. 80, No. 10, 2016, p. 2081-2088.

Research output: Contribution to journalReview article

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