Biomarkers for Vascular Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biomarkers".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11039

Special Issue Editors

Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada
Interests: biomarkers; vascular disease
Special Issues, Collections and Topics in MDPI journals
1. Division of Vascular Surgery, St. Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, ON M5B 1W8, Canada
2. Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada
Interests: vascular surgery; peripheral arterial disease; biomarkers; prognostication; abdominal aortic aneurysm; thrombosis; atherosclerosis
Special Issues, Collections and Topics in MDPI journals
Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
Interests: biomarkers; vascular disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomarkers are an integral part of clinical practice, with utility in diagnosing, monitoring, or predicting different diseases. While biomarkers have been extensively researched for many different medical conditions, vascular diseases such as peripheral arterial disease (PAD), abdominal aortic aneurysm (AAA), and carotid artery stenosis (CAS), remain an exception as researchers are yet to discover and commercialize clinically validated and robust biomarkers for these diseases. Due to the prevalent medical mismanagement of vascular patients, physicians and clinical guidelines have repeatedly called for research into disease-specific biomarkers as they have the potential to significantly augment the care and quality of life of patients with vascular diseases.

As such, the focus of this Special Issue will be on recent advances regarding different potential biomarkers of different vascular diseases. Discovery and validation studies investigating biomarkers of exposure (i.e., for prediction purposes) or biomarkers of disease (i.e., for diagnostic purposes) will be considered. Interested authors are also encouraged and welcome to submit original research or review articles. Finally, a broad overview of the most promising vascular-diseases-specific candidate biomarkers that are able to overcome the clinical challenges associated with PAD will be highlighted.

Prof. Dr. Ori D. Rotstein
Dr. Mohammad Qadura
Dr. Muzammil Syed
Guest Editors

Manuscript Submission Information

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Keywords

  • peripheral arterial disease
  • abdominal aortic aneurysm
  • carotid artery stenosis
  • biomarkers

Related Special Issue

Published Papers (6 papers)

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Research

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16 pages, 3258 KiB  
Article
Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis
by Melody Chemaly, David Marlevi, Maria-Jesus Iglesias, Mariette Lengquist, Malin Kronqvist, Daniel Bos, Dianne H. K. van Dam-Nolen, Anja van der Kolk, Jeroen Hendrikse, Mohamed Kassem, Ljubica Matic, Jacob Odeberg, Margreet R. de Vries, M. Eline Kooi and Ulf Hedin
Biomolecules 2023, 13(6), 882; https://doi.org/10.3390/biom13060882 - 24 May 2023
Viewed by 1623
Abstract
Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. Objective: We explored the biomarker potential of plasma BLVRB through (1) [...] Read more.
Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. Objective: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. Methods: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Results: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092–2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). Conclusions: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability. Full article
(This article belongs to the Special Issue Biomarkers for Vascular Disease)
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14 pages, 2067 KiB  
Article
Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis
by Jianqiang Wu, Wei Wang, Ting Xie, Zhaoran Chen, Lei Zhou, Xiaohong Song, Haoxuan Kan, Yanze Lv, Lianglin Wu, Fangda Li, Dan Yang, Yuexin Chen, Bao Liu and Yuehong Zheng
Biomolecules 2022, 12(12), 1853; https://doi.org/10.3390/biom12121853 - 12 Dec 2022
Cited by 1 | Viewed by 1421
Abstract
Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in the aging population. Currently, there are no approved diagnostic biomarkers or therapeutic drugs for AAA. We aimed to identify novel plasma biomarkers or potential therapeutic targets for AAA using a [...] Read more.
Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in the aging population. Currently, there are no approved diagnostic biomarkers or therapeutic drugs for AAA. We aimed to identify novel plasma biomarkers or potential therapeutic targets for AAA using a high-throughput protein array-based method. Proteomics expression profiles were investigated in plasma from AAA patients and healthy controls (HC) using 440-cytokine protein array analysis. Several promising biomarkers were further validated in independent cohorts using enzyme-linked immunosorbent assay (ELISA). Thirty-nine differentially expressed plasma proteins were identified between AAA and HC. Legumain (LGMN) was significantly higher in AAA patients and was validated in another large cohort. Additionally, “AAA without diabetes” (AAN) patients and “AAA complicated with type 2 diabetes mellitus” (AAM) patients had different cytokine expression patterns in their plasma, and nine plasma proteins were differentially expressed among the AAN, AAM, and HC subjects. Delta-like protein 1 (DLL1), receptor tyrosine-protein kinase erbB-3 (ERBB3), and dipeptidyl peptidase 4 (DPPIV) were significantly higher in AAM than in AAN. This study identified several promising plasma biomarkers of AAA. Their role as therapeutic targets for AAA warrants further investigation. Full article
(This article belongs to the Special Issue Biomarkers for Vascular Disease)
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12 pages, 850 KiB  
Article
A Synergistic Effect between Plasma Dickkopf-1 and Obstructive Coronary Artery Disease on the Prediction of Major Adverse Cardiac Events in Patients with Angina: An Observational Study
by Yu-Hsuan Li, Min-Huan Wu, Wen-Jane Lee and I-Te Lee
Biomolecules 2022, 12(10), 1408; https://doi.org/10.3390/biom12101408 - 02 Oct 2022
Viewed by 1133
Abstract
The canonical β-catenin-dependent wingless (Wnt) pathway is associated with endothelial function. We examined the effect of plasma dickkopf-1 (DKK-1), an inhibitor of the Wnt pathway, on the prediction of major adverse cardiac events (MACEs). We enrolled patients who had undergone selective coronary angiography [...] Read more.
The canonical β-catenin-dependent wingless (Wnt) pathway is associated with endothelial function. We examined the effect of plasma dickkopf-1 (DKK-1), an inhibitor of the Wnt pathway, on the prediction of major adverse cardiac events (MACEs). We enrolled patients who had undergone selective coronary angiography for angina. DKK-1 levels were determined using plasma collected at the outpatient visit after fasting. MACEs served as the primary endpoint. All 470 enrolled patients were divided into four groups according to their median plasma DKK-1 levels and the presence of obstructive coronary artery disease (CAD). Forty-eight patients reached the primary endpoint during a median follow-up time of 4.8 years. Kaplan–Meier survival analysis indicated that the group with high DKK-1 and obstructive CAD had a significantly higher mortality rate than the other three groups (log-rank test p = 0.001). Compared with the low plasma DKK-1 without significant coronary obstruction group, the high DKK-1 with obstructive CAD group had a hazard ratio of 10.640 (95% confidence interval: 1.350–83.874) for MACEs, as determined by multivariable Cox proportional hazard regression analysis. In conclusion, we observed a synergistic effect between high plasma DKK-1 and obstructive CAD on the prediction of MACEs in patients with angina. Full article
(This article belongs to the Special Issue Biomarkers for Vascular Disease)
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11 pages, 802 KiB  
Article
Urinary Cystatin C Has Prognostic Value in Peripheral Artery Disease
by Ben Li, Abdelrahman Zamzam, Muzammil H. Syed, Niousha Jahanpour, Shubha Jain, Rawand Abdin and Mohammad Qadura
Biomolecules 2022, 12(7), 860; https://doi.org/10.3390/biom12070860 - 21 Jun 2022
Cited by 4 | Viewed by 1849
Abstract
Despite its association with adverse outcomes, peripheral artery disease (PAD) remains undertreated. Cystatin C is elevated in patients with renal disease and may be a marker of cardiovascular disease. We examined the prognostic ability of urinary Cystatin C (uCystatinC) in predicting adverse PAD-related [...] Read more.
Despite its association with adverse outcomes, peripheral artery disease (PAD) remains undertreated. Cystatin C is elevated in patients with renal disease and may be a marker of cardiovascular disease. We examined the prognostic ability of urinary Cystatin C (uCystatinC) in predicting adverse PAD-related events. In this prospective case-control study, urine samples were collected from patients with PAD (n = 121) and without PAD (n = 77). The cohort was followed for 2 years. uCystatinC was normalized to urinary creatinine (uCr) (uCystatinC/uCr; μg/g). The primary outcome was major adverse limb event (MALE; composite of vascular intervention (open or endovascular) or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI ≥ 0.15). Multivariable Cox regression and Kaplan–Meier analyses were performed to assess the prognostic value of uCystatinC/uCr with regards to predicting MALE and worsening PAD status. Our analysis demonstrated that patients with PAD had significantly higher median [IQR] uCystatinC/uCr levels (24.9 μg/g [14.2–32.9] vs. 20.9 μg/g [11.1–27.8], p = 0.018). Worsening PAD status and MALE were observed in 39 (20%) and 34 (17%) patients, respectively. uCystatinC/uCr predicted worsening PAD status with a hazard ratio (HR) of 1.78 (95% CI 1.12–2.83, p = 0.015), which persisted after controlling for baseline demographic and clinical characteristics (adjusted HR 1.79 [95% CI 1.11–2.87], p = 0.017). Patients with high uCystatinC/uCr had a lower 2-year freedom from MALE (77% vs. 89%, p = 0.025) and worsening PAD status (63% vs. 87%, p = 0.001). Based on these data, higher uCystatinC/uCr levels are associated with adverse PAD-related events and have prognostic value in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management. Full article
(This article belongs to the Special Issue Biomarkers for Vascular Disease)
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Review

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32 pages, 8397 KiB  
Review
Novel Imaging-Based Biomarkers for Identifying Carotid Plaque Vulnerability
by Verónica Fernández-Alvarez, Miriam Linares-Sánchez, Carlos Suárez, Fernando López, Orlando Guntinas-Lichius, Antti A. Mäkitie, Patrick J. Bradley and Alfio Ferlito
Biomolecules 2023, 13(8), 1236; https://doi.org/10.3390/biom13081236 - 10 Aug 2023
Cited by 1 | Viewed by 1709
Abstract
Carotid artery disease has traditionally been assessed based on the degree of luminal narrowing. However, this approach, which solely relies on carotid stenosis, is currently being questioned with regard to modern risk stratification approaches. Recent guidelines have introduced the concept of the “vulnerable [...] Read more.
Carotid artery disease has traditionally been assessed based on the degree of luminal narrowing. However, this approach, which solely relies on carotid stenosis, is currently being questioned with regard to modern risk stratification approaches. Recent guidelines have introduced the concept of the “vulnerable plaque,” emphasizing specific features such as thin fibrous caps, large lipid cores, intraplaque hemorrhage, plaque rupture, macrophage infiltration, and neovascularization. In this context, imaging-based biomarkers have emerged as valuable tools for identifying higher-risk patients. Non-invasive imaging modalities and intravascular techniques, including ultrasound, computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have played pivotal roles in characterizing and detecting unstable carotid plaques. The aim of this review is to provide an overview of the evolving understanding of carotid artery disease and highlight the significance of imaging techniques in assessing plaque vulnerability and informing clinical decision-making. Full article
(This article belongs to the Special Issue Biomarkers for Vascular Disease)
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Other

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12 pages, 1243 KiB  
Systematic Review
Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
by Suyi Xie, Qi Li, Andrea O. Y. Luk, Hui-Yao Lan, Paul K. S. Chan, Antoni Bayés-Genís, Francis K. L. Chan and Erik Fung
Biomolecules 2022, 12(7), 934; https://doi.org/10.3390/biom12070934 - 04 Jul 2022
Cited by 5 | Viewed by 2645
Abstract
Background: Growth differentiation factor 15 (GDF-15) is a homeostatic cytokine that regulates neural and cardio-metabolic functions, and its release is increased in response to stress, injury, and inflammation. In patients with coronary artery disease and heart failure (HF), three separate meta-analyses have found [...] Read more.
Background: Growth differentiation factor 15 (GDF-15) is a homeostatic cytokine that regulates neural and cardio-metabolic functions, and its release is increased in response to stress, injury, and inflammation. In patients with coronary artery disease and heart failure (HF), three separate meta-analyses have found that elevated circulating GDF-15 was predictive of major adverse cardiovascular events (MACE), but none has evaluated its effects on incident MACE including HF and mortality hazard in type 2 diabetes. Methods: MEDLINE, EMBASE, and Scopus databases were queried. Articles that met the predefined eligibility criteria, including prospective studies that reported adjusted hazard ratios (aHRs), were selected according to the Cochrane Handbook and PRISMA guidelines. Study endpoints were (1) MACE including HF, and (2) all-cause mortality. Different GDF-15 concentration measurements were harmonized using a validated mathematical approach to express log2-transformed values in per standard deviation (SD). Study heterogeneity (I2), quality, and bias were assessed. Results: 19354 patients in 8 prospective studies were included. In 7 studies that reported 4247 MACE among 19200 participants, the incident rate was 22.1% during a median follow-up of 5.6 years. It was found that four of eight studies included HF decompensation or hospitalization as a component of MACE. In 5 studies that reported all-cause mortality, 1893 of 13223 patients died, at an incidence rate of 15.1% over 5.0 years. Of note, each 1 SD increase of log2[GDF-15] was associated with aHRs of 1.12 (1.09–1.15, I2 = 5%, p < 0.000001) and 1.27 (1.11–1.46, I2 = 86%, p = 0.00062) and for MACE and all-cause mortality, respectively. Conclusion: Elevated circulating level of GDF-15 was robustly predictive of MACE in patients with T2D but its prognostic significance in the prediction of mortality requires further studies. Full article
(This article belongs to the Special Issue Biomarkers for Vascular Disease)
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