Diagnostic value of using exosome‑derived cysteine‑rich protein 61 as biomarkers for acute coronary syndrome

Abstract

Acute coronary syndrome (ACS) is the main manifestation of cardiovascular disease and the primary cause of adult hospitalization in China. There is an urgent demand for novel biomarkers for the diagnosis of ACS. Although plasma cysteine-rich protein 61 (Cyr61) has been previously reported to be accurate for ACS diagnosis, the accuracy of exosomal Cyr61 in ACS diagnosis remains unknown. In the present study, the aim was to assess the potential of applying exosomal Cyr61 in ACS diagnosis and to explore the role of Cyr61 in vascular remodeling in vitro. The abundance of Cyr61 in plasma-derived exosomes from patients with unstable angina pectoris (UAP), acute myocardial infarction (AMI) patients in addition to those isolated from healthy individuals were detected using an ELISA kit. The association between exosomal Cyr61 levels and clinical characteristics of ACS patients was analyzed through χ 2 test, Fisher's exact test and Student's t-test. Receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of using exosomal Cyr61 as a biomarker of ACS diagnosis. Furthermore, independent predictors of the existence of ACS were investigated through a multivariate analysis. Subsequently, the role of Cyr61 on vascular remodeling was evaluated in vascular smooth muscle cells (VSMCs) upon oxidized low-density lipoprotein (ox-LDL) treatment by performing Cyr61 knockdown, Cell Counting Kit-8, flow cytometry and Transwell assays. Exosomal Cyr61 expression was found to be significantly elevated in patients with ACS compared with that in healthy individuals. In addition, exosomal Cyr61 levels were associated with sex, family history of ACS and glucose levels. ROC curve analyzes revealed that exosomal Cyr61 expression could be used to differentiate patients with UAP, AMI and ACS from healthy individuals. Furthermore, exosomal Cyr61 levels were independently correlated with the existence of ACS. In vitro, Cyr61 expression was demonstrated to be significantly increased in VSMCs after ox-LDL exposure in a concentration-and time-dependent manner. Functionally, the elevated cell viability and migration of VSMCs induced by ox-LDL were partially but significantly inhibited by Cyr61 knockdown. By contrast, knocking down Cyr61 expression significantly elevated the apoptosis rate of VSMCs compared with that in the ox-LDL-treated group. In conclusion, data from the present study suggest that Cyr61 serve a regulatory role in vascular remodeling in vitro, where exosomal Cyr61 levels may represent a promising biomarker for ACS diagnosis.

Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles

“…Li et al . showed that the elevated amount of CYR61 in circulating EVs is associated with acute coronary syndrome 56 . Besides, the level of Gap junction alpha-1 protein, also known as Connexin-43 (GJA1, CX43) is decreased in circulating and CM EVs after myocardial infarction 57 .…”

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

“… 225 Li et al. 226 also found that increased expression of plasma exosome‐derived cysteine‐rich protein 61 (Cyr61) was associated with the acute coronary syndrome (ACS) and could be used in the diagnosis and prognosis of ACS. In addition, observation of urinary UMOD levels can be used as an early diagnostic biomarker for myocardial infarction.…”

Recent Advances of Using Exosomes as Diagnostic Markers and Targeting Carriers for Cardiovascular Disease

“…The sensitivity of invasive CTA detection reaches 0.92 (sensitivity 92%, specificity 75%), but the sensitivity and specificity of other methods are poor (e.g., hs-cTnT, sensitivity 66.7%, specificity 84.2%). The detection ability and diagnostic efficacy of noncoding RNA (ncRNAs) and exosomes for CAD (e.g., Exos-Cyr61, sensitivity 48–57.5%, specificity 92–94%) are greater than those for ECG (sensitivity 29%, specificity 67%) and close to or higher than those with the Holter test (sensitivity 65%, specificity 90%) and transthoracic echocardiography (sensitivity 79%, specificity 80%) . It is reported that the sensitivity of exo-miR-942-5p, exo-miR-149-5p, and exo-miR-32-5p reaches 70–85% and the specificity reaches 62–85.7% .…”