Systemic Biomarkers and Unique Pathways in Different Phenotypes of Heart Failure with Preserved Ejection Fraction

Abstract

Heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure cases. It is a heterogeneous condition with poorly understood pathogenesis. Here, we aimed to identify unique pathogenic mechanisms in acute and chronic HFpEF and hypertrophic cardiomyopathy (HCM). We performed unbiased, comprehensive proteomic analyses of plasma samples from gender- and BMI-matched patients with acute HFpEF (n = 8), chronic HFpEF (n = 9) and HCM (n = 14) using liquid chromatography–mass spectrometry. Distinct molecular signatures were observed in different HFpEF forms. Clusters of biomarkers differentially abundant between HFpEF forms were predominantly associated with microvascular inflammation. New candidate protein markers were also identified, including leucine-rich alpha-2-glycoprotein 1 (LRG1), serum amyloid A1 (SAA1) and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Our study is the first to apply systematic, quantitative proteomic screening of plasma samples from patients with different subtypes of HFpEF and identify candidate biomarkers for improved management of acute and chronic HFpEF and HCM.

Plasma leucine-rich α-2 glycoprotein 1 in ST-elevation myocardial infarction: vertical variation, correlation with T helper 17/regulatory T ratio, and predictive value on major adverse cardiovascular events

“…Several bioinformatic analyses have shown that LRG1 may serve as a useful biomarker in cardiovascular diseases ( 20 – 23 ). For instance, one study demonstrated that LRG1 is elevated in patients with acute coronary syndrome compared with healthy controls ( 20 ).…”

“…Several bioinformatic analyses have shown that LRG1 may serve as a useful biomarker in cardiovascular diseases (20)(21)(22)(23).…”

FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility

“…However, its diagnostic or pathogenic role has not previously been demonstrated in HF. In light of these important functions associated with FKBPL, it is likely that it may have a role in the development of HF-particularly HFpEF-since inflammation and microvascular dysfunction are hallmark features of HFpEF [14]. Thus, this study evaluated the role of FKBPL in the development of cardiac hypertrophy and HFpEF using in vitro models of cardiomyoblasts exposed to a hypertensive stimulus, angiotensin-II (Ang-II), and/or the FKBPL mimetic AD-01, as well as human plasma samples from people with different forms of HFpEF and controls.…”