Abstract Background Myeloid-derived growth factor (MYDGF) was observed to increase following acute myocardial infarction (MI) in both patients and animal models. Animal studies further demonstrated a critical role of MYDGF in tissue repair post-MI and protection against pressure overload-induced heart failure (HF). However, the understanding of endogenous MYDGF expression in HF patients remains limited. Purpose To explore the relationship between endogenous MYDGF levels and clinical characteristics of HF patients enrolled in the EMPEROR trials, and to assess the impact of empagliflozin on plasma MYDGF expression. Methods Relative quantification of MYDGF by Olink® Explore 3072 proteomics was performed in plasma samples from EMPEROR Reduced (N=580) and Preserved (N=535) trial participants at baseline, week 12, and week 52. Multiple linear regression models, adjusted for age, sex and clinical covariates, were used to assess associations with clinical characteristics. Mixed models for repeated measures evaluated the treatment effect of empagliflozin and a landmark analysis assessed the association between change in plasma MYDGF from baseline and clinical outcome. Spearman correlation analysis followed by a bioinformatics analysis was conducted to construct a network of evidence-based interactions between MYDGF and the remaining 2154 proteins. Results The pooled analysis, including 556 patients on placebo and 559 on empagliflozin from both EMPEROR trials, showed a positive association between MYDGF and female sex (ß estimate± Standard Error: 0.216±0.093, p=0.020), body mass index (0.015±0.008, p=0.048) and triglycerides concentration (0.002±0.0005, p=0.0003) and a negative association with eGFR (−0.011±0.003, p0.0001). Treatment with empagliflozin demonstrated an increase in MYDGF from baseline at week 12 (0.159±0.047, p=0.001) but not at week 52 (0.064±0.058, p=0.271). No association was found between baseline MYDGF concentration or the increase at 12-weeks with CV death or first HF hospitalization and renal composite endpoint. The correlation analysis identified 502 proteins correlated to MYDGF, with a Spearman correlation coefficient ≥ 0.7 and a false discovery rate ≤ 0.01. Subsequent network analysis revealed four proteins with first level interaction with MYDGF: Acyl-coenzyme A thioesterase 13, Hippocalcin-like protein 1, Large proline-rich protein BAG6, and Forkhead box protein O1, involved in lipid metabolism pathways, fatty acid activation and mitochondrial beta-oxidation. Conclusions This study identified significant associations between plasma MYDGF expression and clinical characteristics such as female sex, body mass index, triglycerides concentration, and eGFR in HF patients. Empagliflozin treatment increased MYDGF levels at 12 weeks only with no significant impact on clinical outcomes. Bioinformatic analyses revealed interactions of MYDGF with four proteins involved in lipid metabolism and mitochondrial function, warranting further investigation.
Panova-Noeva et al. (Sat,) studied this question.
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