Heart failure (HF) is a progressive disease process that is accompanied by increasing LV remodeling and LV dysfunction. Although the precise mechanisms responsible for the progression of HF are unknown, there is evidence that over-expression of TNF- alpha, a proinflammatory cytokine, can produce LV remodeling and contractile dysfunction. Also circulating levels of TNF-alpha are 2-8 folds higher in patients with HF compared to normal subjects. The focus of this research is to identify the mechanisms of TNF-alpha function. Because myocardial energetics plays a central role in supporting contractile function and is known to be impaired in the failing heart, the primary goal of this research is to define the consequences of over-expressing TNF-alpha on cardiac energetics and contractile function. Preliminary data show the primary energy reserve compound of the heart, phosphocreatine (PCr), is approximately 40 percent lower in hearts which over-express TNF-alpha. In this research the hypothesis: Cardiac restricted expression of TNF-alpha causes a decrease in contractile reserve by limiting the energy reserve of the heart will be tested.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL010435-01
Application #
6208602
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
2000-08-10
Project End
Budget Start
2000-08-10
Budget End
2001-08-09
Support Year
1
Fiscal Year
2000
Total Cost
$40,936
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Javadpour, Maryam M; Tardiff, Jil C; Pinz, Ilka et al. (2003) Decreased energetics in murine hearts bearing the R92Q mutation in cardiac troponin T. J Clin Invest 112:768-75