In the US, heart failure affects approximately eight million people, carries a poor prognosis, and represents the single largest healthcare cost for people over 65 years old. Most heart failure therapies rely on blocking the deleterious effects of stress hormones on the heart, but therapies aimed at repairing failing heart muscles are lacking. The lab directed by Nora Eccles Harrison Presidential Endowed Chair Robin Shaw, MD, PhD, and Nora Eccles Harrison Cardiovascular Research & Training Institute (CVRTI) investigators, have identified an architectural protein (cBIN1) of heart muscle cells that organizes the intracellular signalizing network responsible for heart muscle contraction and relaxation. They found that lowering cBIN1 caused heart failure progression, and that, in animal models, replacement of cBIN1 by gene therapy rescued failing heart muscle and prevented death. Furthermore, they devised a cBIN1 blood test that can predict hospitalization and death caused by heart failure in patients. Shaw and his team are now preparing for preclinical development of a cBIN1-directed therapy for heart failure. Successful development of such a therapy will significantly improve the lives of Americans and economics of our health care system.
BIN1 localizes the L-type calcium channel to cardiac T-tubules. Hong, T.T., et al., PLoS Biol. 2010 February 16; 8(2):e1000312.
BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Hong, T.T., et al., Heart Rhythm. 2012 May;9(5):812.
Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy. Hong, T.T., et al., Heart Rhythm. 2012 June;9(6):961.
Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia. Hong, T., et al., Nat Med, 2014 June;20(6):624.
The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles. Xu, B., et al., PLoS Biol. 2017 August 14;15(8):e2002354.
Association of a novel diagnostic biomarker, the plasma cardiac bridging integrator 1 score, with heart failure with preserved ejection fraction and cardiovascular hospitalization. Nikolova, A.P., et al., JAMA Cardiol. 2018 December 1;3(12):1206.
In mice subjected to chronic stress, exogenous cBIN1 preserves calcium-handling machinery and cardiac function. Liu, Y., et al., JACC Basic Transl Sci. 2020 May 13;5(6):561.
cBIN1 score (cs) identifies ambulatory HFrEF patients and predicts cardiovascular events. Hitzeman, T.C., et al., Front Physiol. 2020 May 25;11:503.