title: Chronic heart failure: Ca(2+), catabolism, and catastrophic cell death.
abstract: Robust successes have been achieved in recent years in conquering the acutely lethal manifestations of heart disease. Many patients who previously would have died now survive to enjoy happy and productive lives. Nevertheless, the devastating impact of heart disease continues unabated, as the spectrum of disease has evolved with new manifestations. In light of this ever-evolving challenge, insights that culminate in novel therapeutic targets are urgently needed. Here, we review fundamental mechanisms of heart failure, both with reduced (HFrEF) and preserved (HFpEF) ejection fraction. We discuss pathways that regulate cardiomyocyte remodeling and turnover, focusing on Ca(2+) signaling, autophagy, and apoptosis. In particular, we highlight recent insights pointing to novel connections among these events. We also explore mechanisms whereby potential therapeutic approaches targeting these processes may improve morbidity and mortality in the devastating syndrome of heart failure.
authors.affiliation: Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Altamirano
authors.affiliation: Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: joseph.hill@utsouthwestern.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hill
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002908:Chronic Disease; D006333:Heart Failure / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology
chemical_list: D002118:Calcium
keywords: Apoptosis; Autophagy; Calcium homeostasis; Heart failure; Remodeling