title: Heart failure with preserved ejection fraction: molecular pathways of the aging myocardium.
abstract: Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, HFpEF is now as common as heart failure with reduced ejection fraction. We now have many successful treatments for heart failure with reduced ejection fraction, while specific treatment options for HFpEF patients remain elusive. The lack of treatments for HFpEF reflects our very incomplete understanding of this constellation of diseases. There are many pathophysiological factors in HFpEF, but aging appears to play an important role. Here, we propose that aging of the myocardium is itself a specific pathophysiological process. New insights into the aging heart, including hormonal controls and specific molecular pathways, such as microRNAs, are pointing to myocardial aging as a potentially reversible process. While the overall process of aging remains mysterious, understanding the molecular pathways of myocardial aging has never been more important. Unraveling these pathways could lead to new therapies for the enormous and growing problem of HFpEF.
authors.affiliation: From the Department of Stem Cell and Regenerative Biology, Harvard University, Brigham Regenerative Medicine Center, Cambridge, MA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA; and Harvard Stem Cell Institute, Cambridge, MA.
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Loffredo
authors.affiliation: From the Department of Stem Cell and Regenerative Biology, Harvard University, Brigham Regenerative Medicine Center, Cambridge, MA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA; and Harvard Stem Cell Institute, Cambridge, MA.
authors.forename: Andriana P
authors.initials: AP
authors.lastname: Nikolova
authors.affiliation: From the Department of Stem Cell and Regenerative Biology, Harvard University, Brigham Regenerative Medicine Center, Cambridge, MA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA; and Harvard Stem Cell Institute, Cambridge, MA.
authors.forename: James R
authors.initials: JR
authors.lastname: Pancoast
authors.affiliation: From the Department of Stem Cell and Regenerative Biology, Harvard University, Brigham Regenerative Medicine Center, Cambridge, MA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA; and Harvard Stem Cell Institute, Cambridge, MA. RLee@Partners.org.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000375:Aging / Q000502:physiology*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D003971:Diastole; D005355:Fibrosis; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology; D035683:MicroRNAs / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D037761:Sirtuins / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology*; D016615:Telomere
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C513323:RGN protein, human; D017869:Cyclic GMP-Dependent Protein Kinases; D020782:Matrix Metalloproteinases; C516592:SIRT6 protein, human; D037761:Sirtuins
keywords: aging; diastolic dysfunction; heart failure, diastolic