About one in four myocardial infarction (MI) patients progress to develop congestive heart failure, which has a 5-year mortality rate of 50%. The goal of this project is to understand post-MI roles of matrix metalloproteinase-12 (MMP-12) by establishing how MMP-12 serves as a resolution promoting factor to stimulate the transition from inflammation to repair. We hypothesize that MMP-12 regulates individual neutrophil, macrophage, and fibroblast physiology to promote the resolution of post-MI inflammation and stimulate repair.
Our specific aims will explore the mechanism whereby MMP-12 turns off pro- inflammation (aim 1), initiates anti-inflammation (aim 2), and promotes repair (aim 3). Innovation lies in the evaluation of MMP-12 post-MI to connect early cell functions to late remodeling outcomes and in the integration of multi-discipline approaches to explore the mechanisms whereby MMP-12 regulates resolution. This study will drive forward the understanding of the molecular basis of LV remodeling and will identify novel intervention targets directed at MMP-12.

Public Health Relevance

Heart failure is the inability of the heart to adequately supply the body with oxygen and is a leading cause of death in the United States. Of the heart failure patients diagnosed each year, 70% have heart failure due to a previous heart attack (myocardial infarction; MI). The main objective of this grant is to use a mouse MI model to understand how the enzyme matrix metalloproteinase-12 (MMP-12) coordinates scar formation in response to MI.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL137319-03
Application #
10087548
Study Section
Myocardial Ischemia and Metabolism Study Section (MIM)
Program Officer
Schwartz, Lisa
Project Start
2019-02-01
Project End
2023-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198