Abstract
Heart failure (HF) screening strategies require biomarkers to predict disease manifestation to aid HF surveillance and management programmes. The aim of this study was to validate a previous proteomics discovery programme that identified Tetranectin as a potential HF biomarker candidate based on expression level changes in asymptomatic patients at future risk for HF development. The initial study consisted of 132 patients, comprising of HF (n = 40), no-HF controls (n = 60), and cardiac surgery patients (n = 32). Serum samples were quantified for circulating levels of Tetranectin and a panel of circulating fibro-inflammatory markers. Cardiac tissue served as a resource to investigate the relationship between cardiac Tetranectin levels and fibrosis and inflammation within the myocardium. An independent cohort of 224 patients with or without HF was used to validate serum Tetranectin levels. Results show that circulating Tetranectin levels are significantly reduced in HF patients (p < 0.0001), and are associated with HF more closely than B-type natriuretic peptide (AUC = 0.97 versus 0.84, p = 0.011). Serum Tetranectin negatively correlated with circulating fibrosis markers, whereas cardiac tissue Tetranectin correlated positively with fibrotic genes and protein within the myocardium. In conclusion, we report for the first time that Tetranectin is a promising HF biomarker candidate linked with fibrotic processes within the myocardium.
Highlights
Heart failure (HF) screening strategies require biomarkers to predict disease manifestation to aid HF surveillance and management programmes
To confirm previous proteomics findings[6], the expression of serum Tetranectin was quantified in a validation cohort, consisting of 100 patients visiting the heart failure and STOP-HF clinics: 60 no heart failure (no-HF) patients and 40 symptomatic HF patients
Results indicate that circulating levels of Tetranectin is reduced by approximately 50% in HF patients compare with asymptomatic controls (Fig. 1a, p < 0.0001)
Summary
Heart failure (HF) screening strategies require biomarkers to predict disease manifestation to aid HF surveillance and management programmes. The aim of this study was to validate a previous proteomics discovery programme that identified Tetranectin as a potential HF biomarker candidate based on expression level changes in asymptomatic patients at future risk for HF development. One biomarker discovery approach that we previously adopted was to examine the coronary sinus proteome of asymptomatic hypertensive patients with high and low risk of future development of HF, based on their BNP levels[6]. Tetranectin, gene name CLEC3B, is a calcium-binding homotrimeric protein from the C-type lectin family of proteins It is primarily found in serum and in the extracellular matrix (ECM) during development, tissue regeneration and cancer, with low levels in normal adult tissue[7,8].
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