title: Heart failure and mitochondrial dysfunction: the role of mitochondrial fission/fusion abnormalities and new therapeutic strategies.
abstract: The treatment of heart failure (HF) has evolved during the past 30 years with the recognition of neurohormonal activation and the effectiveness of its inhibition in improving the quality of life and survival. Over the past 20 years, there has been a revolution in the investigation of the mitochondrion with the development of new techniques and the finding that mitochondria are connected in networks and undergo constant division (fission) and fusion, even in cardiac myocytes. This has led to new molecular and cellular discoveries in HF, which offer the potential for the development of new molecular-based therapies. Reactive oxygen species are an important cause of mitochondrial and cellular injury in HF, but there are other abnormalities, such as depressed mitochondrial fusion, that may eventually become the targets of at least episodic treatment. The overall need for mitochondrial fission/fusion balance may preclude sustained change in either fission or fusion. In this review, we will discuss the current HF therapy and its impact on the mitochondria. In addition, we will review some of the new drug targets under development. There is potential for effective, novel therapies for HF to arise from new molecular understanding.
authors.affiliation: *Molecular and Cellular Cardiology, Department of Medicine, and †Department of Medical Pharmacology, University of California, Davis, Davis, CA; and ‡VA Medical Center, Sacramento, CA.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Knowlton
authors.forename: Le
authors.initials: L
authors.lastname: Chen
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Malik
mesh_terms: D000818:Animals; D015195:Drug Design; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology*; D063154:Mitochondrial Dynamics; D058990:Molecular Targeted Therapy; D032383:Myocytes, Cardiac / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species