Key result
FKBPL concentration was significantly increased in the plasma of patients with HFpEF compared to controls (p < 0.01), though it could not stratify between different forms of HFpEF.
Why the study?
The pathogenesis of HFpEF remains unclear, impeding effective treatments, and the role of the angiogenesis and inflammation mediator FKBPL in HFpEF pathogenesis and as a biomarker had not been investigated.
Does FKBPL and its peptide mimetic AD-01 play a role in the pathogenesis and serve as a biomarker for HFpEF?
Does FKBPL and its peptide mimetic AD-01 play a role in the pathogenesis and serve as a biomarker for HFpEF?
p-value: p=<0.01
FKBPL is elevated in HFpEF patients and its peptide mimetic AD-01 modulates Ang-II-induced cardiomyocyte hypertrophy in vitro, suggesting potential as a biomarker and therapeutic target.
FKBPL may contribute to HFpEF pathogenesis; leaves open whether it is a viable therapeutic target.
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.
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Chhor et al. (2023) studied Heart failure with preserved ejection fraction (HFpEF). FKBPL and its peptide mimetic AD-01 vs. controls was evaluated on FKBPL concentration in human plasma (p=<0.01). FKBPL concentration was significantly increased in the plasma of patients with HFpEF compared to controls (p < 0.01), though it could not stratify between different forms of HFpEF.
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