FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility
Michael Chhor,
Hao Chen,
Djurdja Jerotić,
Milorad Tešić,
Valentina N. Nikolić,
Milan Pavlović,
Rada M. Vučić,
Benjamin Rayner,
Chris J. Watson,
Mark Ledwidge,
Kenneth McDonald,
Tracy Robson,
Kristine C. McGrath,
Lana McClements
Affiliations
Michael Chhor
Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia
Hao Chen
Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia
Djurdja Jerotić
Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Milorad Tešić
Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Valentina N. Nikolić
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Nis, 18000 Nis, Serbia
Milan Pavlović
Department of Internal Medicine—Cardiology, Faculty of Medicine, University of Nis, 18000 Nis, Serbia
Rada M. Vučić
Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
Benjamin Rayner
Inflammation Group, Heart Research Institute, University of Sydney, Sydney, NSW 2006, Australia
Chris J. Watson
Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, UK
Mark Ledwidge
STOP-HF Unit, St. Vincent’s University Hospital, D04 T6F4 Dublin, Ireland
Kenneth McDonald
STOP-HF Unit, St. Vincent’s University Hospital, D04 T6F4 Dublin, Ireland
Tracy Robson
School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
Kristine C. McGrath
Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia
Lana McClements
Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia
Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated—for the first time—FKBPL’s role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p p p p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.
