Identification of Vinculin as a Potential Diagnostic Biomarker for Acute Aortic Dissection Using Label-Free Proteomics

Abstract

Acute aortic dissection (AAD) is an emergent vascular disease. Currently, its diagnosis depends on clinical and radiological investigations but lacking of serum biomarkers. In this study, we aimed to identify potential serum biomarkers for AAD using label-free proteomics approach. A total of 90 serum samples were collected from three groups: patients with acute aortic dissection (AAD, n=30), patients with acute myocardial infarction (AMI, n=30), and healthy controls (n=30), and the first four samples from each group were selected for label-free proteomics analysis. Using label-free approach, a total of 22 differentially expressed proteins were identified in the serum samples of the AAD group, of which 15 were upregulated and 7 were downregulated as compared to the AMI and healthy control groups. The most prominent increased protein was vinculin, which was selected to validate in total samples. The level of vinculin was significantly elevated in AAD patients (15.8 ng/ml, IQR: 9.3-19.9 ng/ml) than that in AMI patients (8.6 ng/ml, IQR:5.3-11.4 ng/ml) and healthy volunteers (5.3 ng/ml, IQR:2.8-7.6 ng/ml), P<0.0001. Furthermore, the concentration of vinculin both increased in type A and B dissection. At the early stage of AAD, vinculin maintained a high level to 48 hours compared with that of AMI. Our study demonstrated that vinculin may play a role in the early diagnosis of AAD.

Acute, Chronic, and Treated Aortic Diseases Present Distinguishable Serum Proteome Fingerprints with Protein Profiles That Correlate with Disease Severity

“…The patient cohort is detailed in Table 1 and includes 7 groups with surgically stabilized dissections Type A and B taken into one group, hence 6 groups are shown in the table. The cohort size is in the range of recently published serum proteomic studies, e.g., investigating acute aortic dissection vs. acute myocardial infarction and healthy controls [ 11 ]. The cohort consists of healthy controls; patients with coronary heart disease (CHD) to represent cases with a non-aortic cardiovascular condition; thoracic aortic aneurysms, chronic type B dissections (see also additional information below), acute aortic dissections, and surgically stabilized aortic dissections (Type A and B).…”

“…Proteomics using liquid chromatography–tandem mass spectrometry (LC-MS/MS) enables the explorative, quantitative profiling of 100 s of serum or plasma proteins from only a few microliters of liquid biopsy. Previous serum proteome studies in the field of aortic diseases largely focused on comparison of selected aortic diseases vs. a set of controls [ 9 , 10 , 11 , 12 ]. The present study focuses on aortic pathologies including true aneurysms chronic Type B dissections and acute aortic syndromes.…”

Diagnostic and Prognostic Value of Neutrophil Extracellular Trap Levels in Patients With Acute Aortic Dissection

“…Several promising biomarkers have emerged. Vinculin, lumican, MMP-12 and high levels of ischemia-modified albumin have been considered potential AAD-related serum markers that may assist in the diagnosis and prediction of the in-hospital mortality of patients with AAD (27)(28)(29)(30). However, most of these biomarkers are still clinically unavailable.…”

Discovery of Diagnostic and Therapeutic Targets For Vascular Injury Induced By Methylglyoxal Using Proteomics

“…Finally, we determined proteins that were dramatically up-or downregulated as a biomarker or drug target based on either the FC (such as accession numbers H7C2W5 or B7Z553), proteins with high connectivity (such as protein accession number A0A2R8Y7V5), or both the FC and proteins with high connectivity, indicating that all biomarkers or therapeutic targets were medically effective.. For example, compared with the negative control, the ratio of protein accession numbers A0A2R8Y7V5 and E9PPA5 were signi cantly downregulated; this indicated that they were injured and could not work after MGX treatment, resulting in a better therapeutic effect if the level of injured proteins is increased. A few proteins (Table 2) have been listed as diagnostic biomarkers in other papers such as protein accession number P01034; however, these studies either focused on other diseases (such as acute aortic dissection and not VI), or did not include MGX treatment [15].…”

“…Second, although new disease pathways involving the Wnt, ErBb, and BMP signaling pathways were determined, further information such as how they contribute to the pathogenesis of VI remains unclear. Finally, several proteins (Table 2) have been listed as diagnostic biomarkers in other papers such as protein accession number P01034; however, they focused on diseases such as acute aortic dissection, rather than MGX induced VI [15].…”