AUTHOR=Ge Yulong , Liu Xiaoqiang , Chen Hangwei , Li Gonghao , Xing Xing , Liu Junyi , Zhang Chunxia , Zhuge Ying , Wang Fang 

TITLE=The serum soluble scavenger with 5 domains levels: A novel biomarker for individuals with heart failure

JOURNAL=Frontiers in Physiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1140856

DOI=10.3389/fphys.2023.1140856

ISSN=1664-042X

ABSTRACT=<p><bold>Background:</bold> We aimed to explore the relationship between the serum Soluble Scavenger with 5 Domains (SSC5D) levels and heart failure (HF).</p><p><bold>Methods and Results:</bold> We retrospectively enrolled 276 patients diagnosed with HF or normal during hospitalization in Shanghai General Hospital between September 2020 and December 2021. Previously published RNA sequencing data were re-analyzed to confirm the expression profile of <italic>SSC5D</italic> in failing and non-failing human and mouse heart tissues. Quantitative real-time polymerase chain reaction assay was used to quantify <italic>Ssc5d</italic> mRNA levels in murine heart tissue after myocardial infarction and transverse aortic constriction surgery. To understand the HF-induced secreted proteins profile, 1,755 secreted proteins were investigated using human dilated cardiomyopathy RNA-seq data, and the results indicated that <italic>SSC5D</italic> levels were significantly elevated in failing hearts compared to the non-failing. Using single-cell RNA sequencing data, we demonstrated that <italic>Ssc5d</italic> is predominantly expressed in cardiac fibroblasts. In a murine model of myocardial infarction or transverse aortic constriction, <italic>Ssc5d</italic> mRNA levels were markedly increased compared with those in the sham group. Similarly, serum SSC5D levels were considerably elevated in the HF group compared with the control group [15,789.35 (10,745.32–23,110.65) pg/mL, 95% CI (16,263.01–19,655.43) vs. 8,938.72 (6,154.97–12,778.81) pg/mL, 95% CI (9,337.50–11,142.93); <italic>p</italic> &lt; 0.0001]. Moreover, serum SSC5D levels were positively correlated with N-terminal pro-B-type natriuretic peptide (R = 0.4, <italic>p</italic> = 7.9e-12) and inversely correlated with left ventricular ejection fraction (R = −0.46, <italic>p</italic> = 9.8e-16).</p><p><bold>Conclusion:</bold> We concluded that SSC5D was a specific response to HF. Serum SSC5D may function as a novel biomarker and therapeutic target for patients with HF.</p>