Heart function is dependent on the proper differentiation and interaction of the different cardiac compartments. Several mouse mutations have resulted in heart failure with thin myocardium and ventricular septal defects that recapitulates congenital heart defeats in humans. Surprisingly, most of these defects are not myocardial-cell-autonomous, since myocardial-specific mutation of these genes is indistinguishable from wild type. Recently, a role for non-muscular tissues has been proposed as a source of paracrine signals that regulate cardiac myocyte survival, in particular, the epicardium is the first cardiac tissue to respond to morphogenic signals such as retinoic acid and may regulate myocyte proliferation. ? ? This proposal is aimed to the detailed analysis of the role of epicardial derivatives in heart development and function. By the use of a genetic methodology, I will impair epicardial function in the mouse -both at the molecular and cellular level - and, analyze the functional consequences of epicardial ablation. Specifically, I propose: 1. To establish the origin and fate of epicardial cells in the mouse. 2.To analyze the contribution of epicardial cells in vitamin A signaling and, 3. To establish the contribution of epicardial cells to the developing mouse heart. Ablation of epicardial cells and their precursors will be achieved by the use of transgenic mice expressing either diphtheria toxin or Ataxin3 under the control of epicardial-specific promoters. ? ? These studies will set the groundwork to determine the specific nature of epicardial-derived paracrine signals to the myocardium, which may provide with new tools to the treatment of heart disease

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065484-03
Application #
6743972
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Schramm, Charlene A
Project Start
2002-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$342,000
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Serpooshan, Vahid; Zhao, Mingming; Metzler, Scott A et al. (2013) The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials 34:9048-55

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