Abstract: The invention concerns the contribution of elevated levels of circulating alsosterone to heart disease and other hyperaldosteronic conditions. Since activation of ?-arrestin 1(?arr1) by the Angiotensin II (AngII) type 1 receptor (AT1R) mediates AngII-induced aldosterone production, ?-arrestin 1(?arr1) is a therapeutic target for heart disease. The invention provides a ?arr1 protein fragment comprising the C-terminus of ?arr1 (?arr1ct; SEQ ID NO:3), compositions containing this protein fragment, and methods of using this protein fragment to reduce elevated levels of aldosterone in heart disease and other hyperaldosteronic conditions by inhibition of ?-arrestin 1(?arr1). These compositions and methods are of therapeutic benefit in chronic heart failure and progression to heart failure after myocardial infarction (MI).

Abstract: The invention provides a therapeutically-effective method for treatment of heart failure (HF), chronic heart failure, and heart failure post myocardial infarction (MI). This method treats heart failure by enhancing cardiac contractility in a patient by activating ?-arrestin 2 to enhance sarco(endo) plasmic reticulum Ca?2 ATPase (SERCA-2a) small ubiquitin-like modifier-ylation (SUMOlation). Thus, ?-arrestin 2 stimulates cardiac function in heart failure via SERCA-2a potentiation. Additionally, the invention provides a composition for increasing cardiac contractility including a ?-1 adrenergic receptor (?-1 AR) ligand that induces ?-arrestin 2 binding to a ?-1 adrenergic receptor.

Abstract: The disclosure describes the contribution of elevated levels of circulating alsosterone to heart disease and other hyperaldosteronic conditions. Since activation of beta-arrestin I (beta.arr-1) by the Angiotensin II (AngII) type 1 receptor (AT1R) mediates AngII-induced aldosterone production, beta-arrestin I (beta.arr-1) is a therapeutic target for heart disease. Specifically, the disclosure provides a beta.arr-1 protein fragment comprising the C-terminus of beta.arr-1 (beta.arr1ct; SEQ ID NO:3), compositions containing this protein fragment, and methods of using this protein fragment to reduce elevated levels of aldosterone in heart disease and other hyperaldosteronic conditions by inhibition of beta-arrestin (beta.arr-1). These compositions and methods are of therapeutic benefit in chronic heart failure and progression to heart failure after myocardial infarction (MI).

Abstract: The present invention relates to compositions and methods for the treatment of failing hearts. More specifically, the present invention provides for the inhibition of G-protein coupled receptor kinase 2 activity in the adrenal gland, which, for example, decreases catecholamine secretion and the sympathetic burden of the failing heart, thereby improving the cardiac adrenergic/inotropic reserve and overall contractile function.