The broad objective of this work is to understand the basis of formation of the ventricular chamber of the heart. This project specifically considers two distinct processes: how do cardiac muscle cells (cardiomyocytes) expand in number (proliferate), and how do coronary blood vessels form. These processes are related by virtue of being controlled by signals from the outer layer of the heart, a cell type called the epicardium. This project seeks to understand the role and mechanistic basis of these signals, primarily utilizing genetically engineered mice, explanted embryonic mouse tissue, and tissue culture cells to conduct this research.

Public Health Relevance

Heart disease is the leading cause of death in the Western world, and is pernicious because damaged adult heart muscle is mostly not able to repair itself and regenerate. Two critical processes that would be needed for successful regeneration include the growth of cardiac muscle and the reformation of a functional vascular supply. It is widely felt that strategies based on normal processes that occur during embryonic heart development will offer the greatest likelihood for successful treatment of adult heart disease. The primary focus of this project is to address how cardiac muscle and coronary vascular formation occur in the embryo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL070123-08A1S1
Application #
8610438
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Schramm, Charlene A
Project Start
2002-07-01
Project End
2016-04-30
Budget Start
2013-02-01
Budget End
2013-04-30
Support Year
8
Fiscal Year
2013
Total Cost
$22,181
Indirect Cost
$8,656
Name
University of Southern California
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Cambier, Linda; Plate, Markus; Sucov, Henry M et al. (2014) Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R-spondin3. Development 141:2959-71
Brade, Thomas; Kumar, Sandeep; Cunningham, Thomas J et al. (2011) Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardial Igf2. Development 138:139-48
Li, Peng; Cavallero, Susana; Gu, Ying et al. (2011) IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development. Development 138:1795-805
Sucov, Henry M; Gu, Ying; Thomas, Simmy et al. (2009) Epicardial control of myocardial proliferation and morphogenesis. Pediatr Cardiol 30:617-25
Kang, Jione; Gu, Ying; Li, Peng et al. (2008) PDGF-A as an epicardial mitogen during heart development. Dev Dyn 237:692-701