We have recently described a new biological phenomenon, we have termed mesenchymal-endothelial- transition (MEndoT), where scar forming cells in the heart, exhibit plasticity and adopt endothelial cell like fates after cardiac injury. Fibroblast derived endothelial cells contributed to post injury neovascularization and disruption of MEndoT worsened post injury neovascularization and repair. In contrast, augmentation of MEndoT decreased fibrosis and enhanced cardiac repair, demonstrating the potential of MEndoT as a novel therapeutic target in acute heart injury. In more chronic forms of cardiac injury such as cardiac hypertrophy, increased neovascularization is a critical part of the cardiac compensatory response. Enhanced neovascularization is seen in the initial compensatory phase while regression of vasculature and increased fibrosis are seen in the maladaptive phase prior to the development of heart failure. Disruption of neovascularization accelerates and enhanced neovascularization delays or retards the development of heart failure after cardiac hypertrophy. However whether mesenchymal-endothelial-transition occurs in cardiac hypertrophy and can serve as a therapeutic target for delaying or retarding the development of heart failure is not well understood. In this proposal we provide preliminary evidence that mesenchymal-endothelial transition occurs in cardiac hypertrophy and interrogate the physiological role of MEndoT in cardiac hypertrophy with gain and loss of function approaches. Our experiments will provide novel insight into the physiological role of MEndoT in cardiac hypertrophy and potentially identify MEndoT as a novel target for retarding heart failure secondary to cardiac hypertrophy.

Public Health Relevance

We have recently identified a new biological phenomenon called mesenchymal-endothelial-transition where scar forming cells in the heart can coaxed to form endothelial cells and demonstrated this to be a novel strategy for decreasing heart fibrosis after acute injury. In this proposal we will determine whether such a strategy is effective in decreasing scarring in the heart after chronic injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL129178-01
Application #
8957848
Study Section
Cardiac Contractility, Hypertrophy, and Failure Study Section (CCHF)
Program Officer
Wong, Renee P
Project Start
2015-08-10
Project End
2019-05-31
Budget Start
2015-08-10
Budget End
2016-05-31
Support Year
1
Fiscal Year
2015
Total Cost
$385,000
Indirect Cost
$135,000
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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