In:
Biomolecules, MDPI AG, Vol. 13, No. 2 ( 2023-02-18), p. 395-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2218-273X
DOI:
10.3390/biom13020395
Language:
English
Publisher:
MDPI AG
Publication Date:
2023
detail.hit.zdb_id:
2701262-1
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