The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study
demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock
protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human
peripheral blood and their association with CVD. In this research, 20 individuals
with heart failure and 26 participants subjected to cardiac stress tests were enrolled.
The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using
Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking
analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly
exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196
for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released
sEVs into the media, and human cardiomyocytes in culture also released sEVs containing
hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in
the blood when cardiac ischemia was induced during the stress test, as well as the
concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1
and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data
provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs
derived from the human cardiomyocyte cell line, and also in those isolated from human
peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers
for heart diseases such as heart failure and cardiac ischemia.
