Valosin Containing Protein as a Specific Biomarker for Predicting the Development of Acute Coronary Syndrome and Its Complication

Abstract

BackgroundAcute coronary syndrome (ACS) consists of a range of acute myocardial ischemia-related manifestations. The adverse events of ACS are usually associated with ventricular dysfunction (VD), which could finally develop to heart failure. Currently, there is no satisfactory indicator that could specifically predict the development of ACS and its prognosis. Valosin-containing protein (VCP) has recently been proposed to protect against cardiac diseases. Hence, we aimed to assess whether VCP in serum can serve as a valuable biomarker for predicting ACS and its complication.MethodsHuman serum samples from 291 participants were collected and classified into four groups based on their clinical diagnosis, namely healthy control (n = 64), ACS (n = 40), chronic coronary syndrome (CCS, n = 99), and nonischemic heart disease (non-IHD, n = 88). Clinical characteristics of these participants were recorded and their serum VCP levels were detected by enzyme-linked immunosorbent assay (ELISA). Association of serum VCP with the development of ACS and its complication VD was statistically studied. Subsequently, GWAS and eQTL analyses were performed to explore the association between VCP polymorphism and monocyte count. A stability test was also performed to investigate whether VCP is a stable biomarker.ResultsSerum VCP levels were significantly higher in the ACS group compared with the rest groups. Besides, the VCP levels of patients with ACS with VD were significantly lower compared to those without VD. Multivariate logistic regression analysis revealed that VCP was associated with both the risk of ACS (P = 0.042, OR = 1.222) and the risk of developing VD in patients with ACS (P = 0.035, OR = 0.513) independently. The GWAS analysis also identified an association between VCP polymorphism (rs684562) and monocyte count, whereas the influence of rs684562 on VCP mRNA expression level was further verified by eQTL analysis. Moreover, a high stability of serum VCP content was observed under different preservation circumstances.ConclusionValosin-containing protein could act as a stable biomarker in predicting the development of ACS and its complication VD.

Serum SELENBP1 and VCL Are Effective Biomarkers for Clinical and Forensic Diagnosis of Coronary Artery Spasm

“…The remaining 52 (13.8%) proteins were specifically expressed, 14 of which were specific to the CAS group, and the remaining 38 proteins were specific to the control group ( Figure 1 B). In particular, the three ERS-related proteins (VCP, LMAN2, and CAPN-1), which we previously showed to associate with CAS-induced acute ischemia [ 16 , 17 ], were among the 52 specific proteins that supported the successful establishment of the CAS provocation model. To capture the greatest possible serum proteins, we used a rigorous criterion (with a fold change ≥2 and adjusted p -value < 0.05) for protein sorting.…”

“…Xanthine oxidoreductase activity, which plays a pivotal role in producing both uric acid and ROS, has also been reported to associate with CAS in clinical patients [ 15 ]. Endoreticulumn stress (ERS)-related secretory proteins such as valosin containing the protein (VCP), a vesicular integral membrane protein 36 (VIP36, also known as LMAN2), and Calpain-1 (CAPN-1) were considered as potential serological biomarkers for diagnosis of CAS-induced acute ischemia in our previous studies [ 16 , 17 ]. These studies led to transitions from a standard yet risky diagnostic strategy to a non-invasive biochemical diagnostic detection.…”

Correlation between Carbonic Anhydrase Isozymes and the Evolution of Myocardial Infarction in Diabetic Patients

“…It has also been observed that there is a direct correlation between CA II activity and diabetes, in the sense that diabetic patients have higher values of this isoenzyme, while CA I isoenzyme, known for its implications in vasoconstriction and vasodilation, has increased activity in all patients with myocardial infarction, regardless of their diabetic status [ 30 , 31 , 32 ]. The high values of CA II are also correlated with the high values of cardiac markers, meaning that the enzyme can also be an indicator of the state of damage to the heart tissue [ 33 ]. A long-term case follow-up study is needed to investigate the incidence of diabetes and cardiovascular complications of the disease [ 34 ].…”

Quantitative Proteomics of Medium-Sized Extracellular Vesicle-Enriched Plasma of Lacunar Infarction for the Discovery of Prognostic Biomarkers

“…There are candidates from the shortlist that have been proposed as potential biomarkers for different types of vascular complications. E.g., serum VCP level was higher in patients with acute coronary syndrome when compared to healthy control or chronic coronary syndrome [ 38 ]. Serum VCP level was increased in myocardial ischemia-induced sudden cardiac deaths when compared to matched control patients who died from non-cardiac causes [ 39 ].…”