CARDIAC RESTRICTED OVEREXPRESSION OF TNF-ALPHA IN HEART

Brigham And Women'S Hospital, Boston MA

Investigators

Linked publications & trials

Abstract

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.