| Autor: |
Chhor M; Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia., Chen H; Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia., Jerotić D; Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia., Tešić M; Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.; Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia., Nikolić VN; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Nis, 18000 Nis, Serbia., Pavlović M; Department of Internal Medicine-Cardiology, Faculty of Medicine, University of Nis, 18000 Nis, Serbia., Vučić RM; Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.; Department of Cardiology, Clinical Centre of Kragujevac, 34000 Kragujevac, Serbia., Rayner B; Inflammation Group, Heart Research Institute, University of Sydney, Sydney, NSW 2006, Australia., Watson CJ; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK., Ledwidge M; STOP-HF Unit, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland.; School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland., McDonald K; STOP-HF Unit, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland.; School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland., Robson T; School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland., McGrath KC; Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia., McClements L; Faculty of Science, School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia.; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK. |
| Abstrakt: |
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 < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated ( p < 0.01-0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL ( p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls ( 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. |
