Abstract: The invention provides methods of treating ischemia/reperfusion injury in a subject. In one example, a method comprises administering a therapeutically effective amount of a pharmaceutical composition that increases levels of Bcl2-associated athanogene 3 (BAG3) polypeptide in ischemic tissue. The invention also provides methods of treating a subject at risk of ischemia/reperfusion injury. In one example, a method comprises administering a therapeutically effective amount of a pharmaceutical composition that increases levels of Bcl2-associated athanogene 3 (BAG3) polypeptide. In the invention methods, in one example, a pharmaceutical composition comprises a nucleic acid encoding BAG3 polypeptide.

Abstract: Bag3 is a multifunctional protein expressed predominantly in the heart, the skeletal muscle, the central nervous system and in many cancers. Although BAG3 was cloned only a decade ago, studies have shown that genetic variants, particularly those that result in haplo-insufficiency, can lead to severe left ventricular dysfunction; however, the full mechanisms responsible have remained obscure. To obviate the influence of heart failure itself on the biology of Bag3, ransgenic mice harboring a single allele knock-out were studied between 8 and 10 weeks of age before any obvious signs of heart failure were evident. The results were surprising and informative. First, it was found that despite a normal phenotype, young Bag3+/? had marked changes in the proteome that were characterized by changes in proteins associated with metabolism and apoptosis. Consistent with this finding, a decrease in the levels of critical proteins charged with maintaining the mitochondrial membrane potential was observed.

Abstract: Compositions are directed to BCL2-associated athanogene 3 (BAG3) molecules and agents which modulate expression of BAG3 molecules. Pharmaceutical composition for administration to patients, for example, patients with heart failure, comprise one or more BAG3 molecules or agents which modulate expression of BAG3. Methods of treatment and identifying candidate therapeutic agents are also provided.

Abstract: Compositions are directed to BCL2-associated athanogene 3 (BAG3) molecules and agents which modulate expression of BAG3 molecules. Pharmaceutical composition for administration to patients, for example, patients with heart failure, comprise one or more BAG3 molecules or agents which modulate expression of BAG3. Methods of treatment and identifying candidate therapeutic agents are also provided.

Abstract: Compositions are directed to BCL2-associated athanogene 3 (BAG3) molecules and agents which modulate expression of BAG3 molecules. Pharmaceutical composition for administration to patients, for example, patients with heart failure, comprise one or more BAG3 molecules or agents which modulate expression of BAG3. Methods of treatment and identifying candidate therapeutic agents are also provided.

Abstract: Identification of BAG3 (Bcl2-associated anthanogene 3) genetic variants were associated with the prevalence non-ischemic or ischemic dilated cardiomyopathy (DCM) and DCM outcomes in individuals of African ancestry.

Abstract: Compositions are directed to BCL2-associated athanogene 3 (BAG3) molecules and agents which modulate expression of BAG3 molecules. Pharmaceutical composition for administration to patients, for example, patients with heart failure, comprise one or more BAG3 molecules or agents which modulate expression of BAG3. Methods of treatment and identifying candidate therapeutic agents are also provided.

Abstract: Compositions for treatment and prevention of ischemia/reperfusion injury include agents that increase levels of the Bcl2-associated athanogene 3 (BAG3). The compositions are administered to a subject suffering from ischemia/reperfusion injury or who is at risk for ischemia/reperfusion injury.

Abstract: The present invention features methods and compositions for treatment of heart failure. The compositions can include an isolated nucleic acid encoding a BAG3 polypeptide or fragment thereof.

Abstract: Compositions are directed to BCL2-associated athanogene 3 (BAG3) molecules and agents which modulate expression of BAG3 molecules. Pharmaceutical composition for administration to patients, for example, patients with heart failure, comprise one or more BAG3 molecules or agents which modulate expression of BAG3. Methods of treatment and identifying candidate therapeutic agents are also provided.

Abstract: The present invention relates to methods for identify subjects for responsiveness to adenosine agonist treatment. Another aspect of the present invention relates to methods to predict a relative infarct size in response to ischemia reperfusion injury. In particular, the present invention relates to methods for to identify responsiveness to adenosine agonist treatment and/or relative infarct size by identifying a sequence differences such as mutations and/or polymorphisms in the human A1 adenosine receptor (A1-AR) gene that alters the stability of the A1-AR mRNA. Other aspect of the present invention relates to methods to identify responsiveness to adenosine agonist treatment and/or relative infarct size by identifying a sequence differences, such as mutations and/or polymorphisms in the human A3 adenosine receptor (A3-AR) gene that alters the A3-AR protein function.

Abstract: The present invention is directed to reduce elevated levels of tumor necrosis factor-alpha (TNF-&agr;) found in a failing heart. The present invention is directed to a composition and method of regulating TNF-&agr; expression in myocardial tissue by treating the myocardial tissue with biological equivalents of endogenous adenosine. A composition and method of using the composition to treat patients with damaged myocardial tissue is provided which increases the cellular availability of adenosine with a resulting decrease of TNF-&agr; levels in the heart. The present invention provides a novel pharmacological intervention program in failing mammalian hearts, and more particularly provides a cardioprotective treatment to patients with congestive heart failure.

Abstract: The present invention is directed to reduce elevated levels of tumor necrosis factor-alpha (TNF-.alpha.) found in a failing heart. The present invention is directed to a composition and method of regulating TNF-.alpha. expression in myocardial tissue by treating the myocardial tissue with biological equivalents of endogenous adenosine. A composition and method of using the composition to treat patients with damaged myocardial tissue is provided which increases the cellular availability of adenosine with a resulting decrease of TNF-.alpha. levels in the heart. The present invention provides a novel pharmacological intervention program in failing mammalian hearts, and more particularly provides a cardioprotective treatment to patients with congestive heart failure.

Abstract: The present invention provides transgenic nonhuman mammals that exhibit elevated levels of tumor necrosis factor alpha in myocardium relative to nontransgenic control mammals, and methods for making transgenic non-human mammals. The invention further provides a method for identifying agents useful in the treatment and prevention of cardiac dysfunction.