Biomarkers of Vascular Diseases 2.0

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 50128

Special Issue Editor


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Guest Editor
Vascular Diseases Center, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy
Interests: chronic venous disorders; venous leg ulcers; neurovascular disease; genetic polymorphism; hemodynamics; cerebral circulation; CCSVI; ultrasound; exercise; PAD
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Special Issue Information

Dear Colleagues,

The arterial, venous and lymphatic components of the human circulation are a fascinating field of research. The physical parameters of blood flow, blood oxygenation, imaging patterns, electric signaling and, of course, circulating and wall molecules are all potential biomarkers to improve our understanding and treatment of vascular disease. The latter is a heterogenous field of medicine, linked with metabolic and inflammatory disorders. In addition, there is a complex cross talk between circulating cells, the coagulation cascade, endothelial cells, and inflammatory cytokines that needs to be further elucidated. Finally, vascular and endovascular surgery, pharmacological therapy, cell therapy and rehabilitative treatments urgently need predictive biomarkers to address indications and monitor the outcome of interventions during follow-up.

Prof. Paolo Zamboni
Guest Editor

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Keywords

  • biomarkers
  • blood flow
  • vascular pharmacology
  • tissue oxygenation
  • electric biosignaling
  • imaging techniques
  • ultrasound
  • inflammation
  • vascular–endovascular surgery
  • wound healing
  • cell therapy
  • exercise
  • vascular rehabilitation
  • metabolism
  • sensors
  • coagulation

Published Papers (14 papers)

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Research

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15 pages, 4557 KiB  
Article
Super-Resolution Ultrasound Imaging Can Quantify Alterations in Microbubble Velocities in the Renal Vasculature of Rats
by Sofie Bech Andersen, Iman Taghavi, Stinne Byrholdt Søgaard, Carlos Armando Villagómez Hoyos, Michael Bachmann Nielsen, Jørgen Arendt Jensen and Charlotte Mehlin Sørensen
Diagnostics 2022, 12(5), 1111; https://doi.org/10.3390/diagnostics12051111 - 28 Apr 2022
Cited by 6 | Viewed by 2097
Abstract
Super-resolution ultrasound imaging, based on the localization and tracking of single intravascular microbubbles, makes it possible to map vessels below 100 µm. Microbubble velocities can be estimated as a surrogate for blood velocity, but their clinical potential is unclear. We investigated if a [...] Read more.
Super-resolution ultrasound imaging, based on the localization and tracking of single intravascular microbubbles, makes it possible to map vessels below 100 µm. Microbubble velocities can be estimated as a surrogate for blood velocity, but their clinical potential is unclear. We investigated if a decrease in microbubble velocity in the arterial and venous beds of the renal cortex, outer medulla, and inner medulla was detectable after intravenous administration of the α1-adrenoceptor antagonist prazosin. The left kidneys of seven rats were scanned with super-resolution ultrasound for 10 min before, during, and after prazosin administration using a bk5000 ultrasound scanner and hockey-stick probe. The super-resolution images were manually segmented, separating cortex, outer medulla, and inner medulla. Microbubble tracks from arteries/arterioles were separated from vein/venule tracks using the arterial blood flow direction. The mean microbubble velocities from each scan were compared. This showed a significant prazosin-induced velocity decrease only in the cortical arteries/arterioles (from 1.59 ± 0.38 to 1.14 ± 0.31 to 1.18 ± 0.33 mm/s, p = 0.013) and outer medulla descending vasa recta (from 0.70 ± 0.05 to 0.66 ± 0.04 to 0.69 ± 0.06 mm/s, p = 0.026). Conclusively, super-resolution ultrasound imaging makes it possible to detect and differentiate microbubble velocity responses to prazosin simultaneously in the renal cortical and medullary vascular beds. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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14 pages, 4810 KiB  
Article
The Role of Early Revascularization and Biomarkers in the Management of Diabetic Foot Ulcers: A Single Center Experience
by Ettore Dinoto, Francesca Ferlito, Manfredi Agostino La Marca, Graziella Tortomasi, Francesca Urso, Salvatore Evola, Giovanni Guercio, Marco Marcianò, David Pakeliani, Guido Bajardi and Felice Pecoraro
Diagnostics 2022, 12(2), 538; https://doi.org/10.3390/diagnostics12020538 - 19 Feb 2022
Cited by 5 | Viewed by 2638
Abstract
Diabetic neuropathy and Peripheral Arterial Disease (PAD) are the main etiological factors in foot ulceration. Herein, we report our experience of diabetic foot ulceration (DFU) management, with an analysis of the relationship between the rate of lower extremity amputation, in persons with infected [...] Read more.
Diabetic neuropathy and Peripheral Arterial Disease (PAD) are the main etiological factors in foot ulceration. Herein, we report our experience of diabetic foot ulceration (DFU) management, with an analysis of the relationship between the rate of lower extremity amputation, in persons with infected DFU, after revascularization procedures performed to prevent major amputation. This study highlights the role of different biomarkers, showing their usefulness and potentiality in diabetic foot ulcer management, especially for the early diagnosis and therapy effectiveness monitoring. A retrospective analysis, from September 2016 to January 2021, of diabetic patients presenting diabetic foot with DFU, was performed. All patients were treated with at least one vascular procedure (endovascular, open, hybrid procedures) targeting PAD lesions. Outcomes measured were perioperative mortality and morbidity. Freedom from occlusion, primary and secondary patency, and amputation rate were registered. A total of 267 patients, with a mean age of 72.5 years, were included in the study. The major amputation rate was 6.2%, minor amputation rate was 17%. In our experience, extreme revascularization to obtain direct flow reduced the rate of amputations, with an increase in ulcer healing. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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17 pages, 3844 KiB  
Article
A Comparison of Magnetic Resonance Imaging Methods to Assess Multiple Sclerosis Lesions: Implications for Patient Characterization and Clinical Trial Design
by Ewart Mark Haacke, Evanthia Bernitsas, Karthik Subramanian, David Utriainen, Vinay Kumar Palutla, Kiran Yerramsetty, Prashanth Kumar, Sean K. Sethi, Yongsheng Chen, Zahid Latif, Pavan Jella, Sara Gharabaghi, Ying Wang, Xiaomeng Zhang, Robert A. Comley, John Beaver and Yanping Luo
Diagnostics 2022, 12(1), 77; https://doi.org/10.3390/diagnostics12010077 - 30 Dec 2021
Cited by 5 | Viewed by 2744
Abstract
Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 [...] Read more.
Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 weighted imaging (T1WI, T2WI), T2 fluid attenuated inversion recovery (FLAIR), magnetization transfer, myelin water fraction, diffusion tensor imaging (DTI), phase-sensitive inversion recovery and susceptibility weighted imaging (SWI), but no study has combined all of these modalities into a single well-controlled investigation. The goals of this study were to: compare different MRI measures for lesion visualization and quantification; evaluate the repeatability of various imaging methods in healthy controls; compare quantitative susceptibility mapping (QSM) with myelin water fraction; measure short-term longitudinal changes in the white matter of MS patients and map out the tissue properties of the white matter hyperintensities using STAGE (strategically acquired gradient echo imaging). Additionally, the outcomes of this study were anticipated to aid in the choice of an efficient imaging protocol reducing redundancy of information and alleviating patient burden. Of all the sequences used, T2 FLAIR and T2WI showed the most lesions. To differentiate the putative demyelinating lesions from inflammatory lesions, the fusion of SWI and T2 FLAIR was used. Our study suggests that a practical and efficient imaging protocol combining T2 FLAIR, T1WI and STAGE (with SWI and QSM) can be used to rapidly image MS patients to both find lesions and study the demyelinating and inflammatory characteristics of the lesions. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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14 pages, 2052 KiB  
Article
Plethysmography System to Monitor the Jugular Venous Pulse: A Feasibility Study
by Antonino Proto, Daniele Conti, Erica Menegatti, Angelo Taibi and Giacomo Gadda
Diagnostics 2021, 11(12), 2390; https://doi.org/10.3390/diagnostics11122390 - 18 Dec 2021
Cited by 6 | Viewed by 5914
Abstract
Cerebral venous outflow is investigated in the diagnosis of heart failure through the monitoring of jugular venous pulse, an indicator to assess cardiovascular diseases. The jugular venous pulse is a weak signal stemming from the lying internal jugular vein and often invasive methodologies [...] Read more.
Cerebral venous outflow is investigated in the diagnosis of heart failure through the monitoring of jugular venous pulse, an indicator to assess cardiovascular diseases. The jugular venous pulse is a weak signal stemming from the lying internal jugular vein and often invasive methodologies requiring surgery are mandatory to detect it. Jugular venous pulse can also be extrapolated via the ultrasound technique, but it requires a qualified healthcare operator to perform the examination. In this work, a wireless, user-friendly, wearable device for plethysmography is developed to investigate the possibility of monitoring the jugular venous pulse non-invasively. The proposed device can monitor the jugular venous pulse and the electrocardiogram synchronously. To study the feasibility of using the proposed device to detect physiological variables, several measurements were carried out on healthy subjects by considering three different postures: supine, sitting, and upright. Data acquired in the experiment were properly filtered to highlight the cardiac oscillation and remove the breathing contribution, which causes a considerable shift in the amplitude of signals. To evaluate the proper functioning of the wearable device for plethysmography, a comparison with the ultrasound technique was carried out. As a satisfactory result, the acquired signals resemble the typical jugular venous pulse waveforms found in literature. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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13 pages, 1653 KiB  
Article
Assessment of Serum Neopterin as a Biomarker in Peripheral Artery Disease
by Agnieszka Zembron-Lacny, Wioletta Dziubek, Anna Tylutka, Eryk Wacka, Barbara Morawin, Katarzyna Bulinska, Malgorzata Stefanska, Marek Wozniewski and Andrzej Szuba
Diagnostics 2021, 11(10), 1911; https://doi.org/10.3390/diagnostics11101911 - 15 Oct 2021
Cited by 4 | Viewed by 1562
Abstract
Neopterin (NPT), a pyrazino-pyrimidine compound mainly produced by activated macrophages, has been regarded as a proinflammatory and proatherosclerotic agent. The study was designed to evaluate NPT level and its interaction with conventional peripheral artery disease (PAD) biomarkers and vascular regenerative potential in severe [...] Read more.
Neopterin (NPT), a pyrazino-pyrimidine compound mainly produced by activated macrophages, has been regarded as a proinflammatory and proatherosclerotic agent. The study was designed to evaluate NPT level and its interaction with conventional peripheral artery disease (PAD) biomarkers and vascular regenerative potential in severe PAD. The study included 59 patients (females n = 17, males n = 42) aged 67.0 ± 8.2 years classified into two groups based on ankle-brachial index (ABI) measurements (ABI ≤ 0.9 n = 43, ABI ≤ 0.5 n = 16). A total of 60 subjects aged 70.4 ± 5.5 years (females n = 42, males n = 18) with ABI > 0.9 constituted a reference group. NPT concentration reached values above 10 nmol/L in patients with PAD, which differed significantly from reference group (8.15 ± 1.33 nmol/L). High levels of CRP > 5 mg/L, TC > 200 mg/dL as well as lipoproteins LDL > 100 mg/dL and non-HDL > 130 mg/dL were found in the same group, indicating the relationship between NPT and conventional atherogenic markers. The endothelial progenitor cells (EPCs) tended toward lower values in patients with ABI ≤ 0.5 when compared to reference group, and inversely correlated with NPT. These findings indicate a crucial role of NPT in atheromatous process and its usefulness in monitoring PAD severity. However, the role of NPT in chronic PAD needs further studies including relatively high number of subjects. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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16 pages, 2934 KiB  
Article
Mathematical Models for Blood Flow Quantification in Dialysis Access Using Angiography: A Comparative Study
by Nischal Koirala and Gordon McLennan
Diagnostics 2021, 11(10), 1771; https://doi.org/10.3390/diagnostics11101771 - 26 Sep 2021
Cited by 2 | Viewed by 2308
Abstract
Blood flow rate in dialysis (vascular) access is the key parameter to examine patency and to evaluate the outcomes of various endovascular interve7ntions. While angiography is extensively used for dialysis access–salvage procedures, to date, there is no image-based blood flow measurement application commercially [...] Read more.
Blood flow rate in dialysis (vascular) access is the key parameter to examine patency and to evaluate the outcomes of various endovascular interve7ntions. While angiography is extensively used for dialysis access–salvage procedures, to date, there is no image-based blood flow measurement application commercially available in the angiography suite. We aim to calculate the blood flow rate in the dialysis access based on cine-angiographic and fluoroscopic image sequences. In this study, we discuss image-based methods to quantify access blood flow in a flow phantom model. Digital subtraction angiography (DSA) and fluoroscopy were used to acquire images at various sampling rates (DSA—3 and 6 frames/s, fluoroscopy—4 and 10 pulses/s). Flow rates were computed based on two bolus tracking algorithms, peak-to-peak and cross-correlation, and modeled with three curve-fitting functions, gamma variate, lagged normal, and polynomial, to correct errors with transit time measurement. Dye propagation distance and the cross-sectional area were calculated by analyzing the contrast enhancement in the vessel. The calculated flow rates were correlated versus an in-line flow sensor measurement. The cross-correlation algorithm with gamma-variate curve fitting had the best accuracy and least variability in both imaging modes. The absolute percent error (mean ± SEM) of flow quantification in the DSA mode at 6 frames/s was 21.4 ± 1.9%, and in the fluoroscopic mode at 10 pulses/s was 37.4 ± 3.6%. The radiation dose varied linearly with the sampling rate in both imaging modes and was substantially low to invoke any tissue reactions or stochastic effects. The cross-correlation algorithm and gamma-variate curve fitting for DSA acquisition at 6 frames/s had the best correlation with the flow sensor measurements. These findings will be helpful to develop a software-based vascular access flow measurement tool for the angiography suite and to optimize the imaging protocol amenable for computational flow applications. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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14 pages, 2574 KiB  
Article
Motor Cortical Activation Assessment in Progressive Multiple Sclerosis Patients Enrolled in Gait Rehabilitation: A Secondary Analysis of the RAGTIME Trial Assisted by Functional Near-Infrared Spectroscopy
by Nicola Lamberti, Fabio Manfredini, Andrea Baroni, Anna Crepaldi, Susanna Lavezzi, Nino Basaglia and Sofia Straudi
Diagnostics 2021, 11(6), 1068; https://doi.org/10.3390/diagnostics11061068 - 09 Jun 2021
Cited by 3 | Viewed by 2563
Abstract
This study aimed to determine cortical activation responses to two different rehabilitative programs, as measured through functional near-infrared spectroscopy (fNIRS). As a secondary analysis of the RAGTIME trial, we studied 24 patients with progressive multiple sclerosis (MS) and severe disability who were randomized [...] Read more.
This study aimed to determine cortical activation responses to two different rehabilitative programs, as measured through functional near-infrared spectroscopy (fNIRS). As a secondary analysis of the RAGTIME trial, we studied 24 patients with progressive multiple sclerosis (MS) and severe disability who were randomized to a regimen of robot-assisted gait training (RAGT) or overground walking (OW). Cortical activation during a treadmill walking task, assessed through fNIRS recordings from the motor and premotor cortexes (M1/PM), was calculated as the area under the curve (AUC) of oxyhemoglobin for each hemisphere and the total area (Tot-OxyAUC). Gait speed, endurance, and balance were also measured, along with five healthy control subjects. At baseline, Tot-OxyAUC during walking was significantly increased in MS patients compared to healthy people and was significantly higher for those with more severe disabilities; it was also inversely correlated with physical performance. After rehabilitation, significant opposite variations in Tot-OxyAUC were observed, with activity levels being increased after OW and decreased after RAGT (+242,080 ± 361,902 and −157,031 ± 172,496 arbitrary units, respectively; p = 0.002), particularly in patients who were trained at a lower speed. Greater reductions in the cortical activation of the more affected hemisphere were significantly related to improvements in gait speed (r = −0.42) and endurance (r = −0.44). Cortical activation, assessed through fNIRS, highlighted the brain activity in response to the type and intensity of rehabilitation. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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17 pages, 1722 KiB  
Article
COVID-19 Vaccine and Death: Causality Algorithm According to the WHO Eligibility Diagnosis
by Cristoforo Pomara, Francesco Sessa, Marcello Ciaccio, Francesco Dieli, Massimiliano Esposito, Giovanni Maurizio Giammanco, Sebastiano Fabio Garozzo, Antonino Giarratano, Daniele Prati, Francesca Rappa, Monica Salerno, Claudio Tripodo, Pier Mannuccio Mannucci and Paolo Zamboni
Diagnostics 2021, 11(6), 955; https://doi.org/10.3390/diagnostics11060955 - 26 May 2021
Cited by 47 | Viewed by 12049
Abstract
The current challenge worldwide is the administration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Even if rarely, severe vascular adverse reactions temporally related to vaccine administration have induced diffidence in the population at large. In particular, researchers worldwide are focusing on [...] Read more.
The current challenge worldwide is the administration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Even if rarely, severe vascular adverse reactions temporally related to vaccine administration have induced diffidence in the population at large. In particular, researchers worldwide are focusing on the so-called “thrombosis and thrombocytopenia after COVID-19 vaccination”. This study aims to establish a practical workflow to define the relationship between adverse events following immunization (AEFI) and COVID-19 vaccination, following the basic framework of the World Health Organization (WHO). Post-mortem investigation plays a pivotal role to support this causality relationship when death occurs. To demonstrate the usefulness and feasibility of the proposed workflow, we applied it to two exemplificative cases of suspected AEFI following COVID-19 vaccination. Based on the proposed model, we took into consideration any possible causality relationship between COVID-19 vaccine administration and AEFI. This led us to conclude that vaccination with ChAdOx1 nCov-19 may cause the rare development of immune thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4), which clinically mimics heparin-induced autoimmune thrombocytopenia. We suggest the adoption of the proposed methodology in order to confirm or rule out a causal relationship between vaccination and the occurrence of AEFI. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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10 pages, 589 KiB  
Article
Serum Anti-Collagen IV IgM and IgG Antibodies as Indicators of Low Vascular Turnover of Collagen IV in Patients with Long-Term Complications of Type 2 Diabetes
by Krasimir Kostov and Alexander Blazhev
Diagnostics 2021, 11(5), 900; https://doi.org/10.3390/diagnostics11050900 - 19 May 2021
Viewed by 2486
Abstract
Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can [...] Read more.
Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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13 pages, 587 KiB  
Article
Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project
by Erasmo Zamarrón-Licona, José Manuel Rodríguez-Pérez, Rosalinda Posadas-Sánchez, Gilberto Vargas-Alarcón, Manuel Alfonso Baños-González, Verónica Marusa Borgonio-Cuadra and Nonanzit Pérez-Hernández
Diagnostics 2021, 11(5), 774; https://doi.org/10.3390/diagnostics11050774 - 26 Apr 2021
Cited by 7 | Viewed by 1885
Abstract
Background: Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events [...] Read more.
Background: Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events in asymptomatic individuals diagnosed with subclinical atherosclerosis (CAC > 0). In this study, our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals. Methods: We analyzed two PCSK9 polymorphisms (rs2479409 and rs615563) in 394 individuals with subclinical atherosclerosis and 1102 healthy controls using real time- polymerase chain reaction (PCR). Results: Under various inheritance models adjusted for different confounding factors, the rs2479409 polymorphism was associated with an increased risk of developing subclinical atherosclerosis (OR = 1.53, P recessive = 0.041). Both polymorphisms were significantly associated with several cardiometabolic parameters. Conclusions: Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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Review

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19 pages, 638 KiB  
Review
The Diagnostic Value of Circulating Biomarkers and Role of Drug-Coated Balloons for In-Stent Restenosis in Patients with Peripheral Arterial Disease
by Nunzio Montelione, Vincenzo Catanese, Antonio Nenna, Mohamad Jawabra, Emanuele Verghi, Francesco Loreni, Francesco Nappi, Mario Lusini, Ciro Mastroianni, Federica Jiritano, Giuseppe Filiberto Serraino, Pasquale Mastroroberto, Francesco Alberto Codispoti, Massimo Chello, Francesco Spinelli and Francesco Stilo
Diagnostics 2022, 12(9), 2207; https://doi.org/10.3390/diagnostics12092207 - 12 Sep 2022
Cited by 4 | Viewed by 1827
Abstract
Peripheral arterial disease (PAD) is an increasingly pathological condition that commonly affects the femoropopliteal arteries. The current fashionable treatment is percutaneous transluminal angioplasty (PTA), often with stenting. However, the in-stent restenosis (ISR) rate after the stenting of the femoropopliteal (FP) district remains high. [...] Read more.
Peripheral arterial disease (PAD) is an increasingly pathological condition that commonly affects the femoropopliteal arteries. The current fashionable treatment is percutaneous transluminal angioplasty (PTA), often with stenting. However, the in-stent restenosis (ISR) rate after the stenting of the femoropopliteal (FP) district remains high. Many techniques have been proposed for the treatment of femoropopliteal ISR, such as intravascular brachytherapy, laser atherectomy, second stenting and drug-coated balloons angioplasty (DCB). DCB showed a significantly lower rate of restenosis and target lesions revascularization (TLR) compared to conventional PTA. However, further studies and multi-center RCTs with dedicated long-term follow-up are needed to verify the true efficiency of this approach. Nowadays, the correlation between PAD and inflammation biomarkers is well known. Multiple studies have shown that proinflammatory markers (such as C-reactive proteins) and the high plasma levels of microRNA could predict the outcomes after stent placement. In particular, circulating microRNA-320a, microRNA-3937, microRNA-642a-3p and microRNA-572 appear to hold promise in diagnosing ISR in patients with PAD, but also as predictors of stent patency. This narrative review intends to summarize the current knowledge on the value of circulating biomarkers as predictors of ISR and to foster the scientific debate on the advantages of using DCB in the treatment of ISR in the FP district. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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15 pages, 1544 KiB  
Review
PBMNCs Treatment in Critical Limb Ischemia and Candidate Biomarkers of Efficacy
by Matilde Zamboni, Massimo Pedriali, Luca Ferretto, Sabrina Scian, Francesca Ghirardini, Riccardo Bozza, Romeo Martini and Sandro Irsara
Diagnostics 2022, 12(5), 1137; https://doi.org/10.3390/diagnostics12051137 - 04 May 2022
Cited by 2 | Viewed by 1844
Abstract
When in critical limb ischemia (CLI) the healing process aborts or does not follow an orderly and timely sequence, a chronic vascular wound develops. The latter is major problem today, as their epidemiology is continuously increasing due to the aging population and a [...] Read more.
When in critical limb ischemia (CLI) the healing process aborts or does not follow an orderly and timely sequence, a chronic vascular wound develops. The latter is major problem today, as their epidemiology is continuously increasing due to the aging population and a growth in the incidence of the underlying diseases. In the US, the mean annualized prevalence of necrotic wounds due to the fact of CLI is 1.33% (95% CI, 1.32–1.34%), and the cost of dressings alone has been estimated at USD 5 billion per year from healthcare budgets. A promising cell treatment in wound healing is the local injection of peripheral blood mononuclear cells (PBMNCs). The treatment is aimed to induce angiogenesis as well to switch inflammatory macrophages, called the M1 phenotype, into anti-inflammatory macrophages, called M2, a phenotype devoted to tissue repair. This mechanism is called polarization and is a critical step for the healing of all human tissues. Regarding the clinical efficacy of PBMNCs, the level of evidence is still low, and a considerable effort is necessary for completing the translational process toward the patient bed site. From this point of view, it is crucial to identify some candidate biomarkers to detect the switching process from M1 to M2 in response to the cell treatment. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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15 pages, 868 KiB  
Review
Biomarkers in EndoVascular Aneurysm Repair (EVAR) and Abdominal Aortic Aneurysm: Pathophysiology and Clinical Implications
by Francesco Stilo, Vincenzo Catanese, Antonio Nenna, Nunzio Montelione, Francesco Alberto Codispoti, Emanuele Verghi, Teresa Gabellini, Mohamad Jawabra, Massimo Chello and Francesco Spinelli
Diagnostics 2022, 12(1), 183; https://doi.org/10.3390/diagnostics12010183 - 13 Jan 2022
Cited by 3 | Viewed by 2761
Abstract
Circulating biomarkers have been recently investigated among patients undergoing endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). Considering the plethora of small descriptive studies reporting potential associations between biomarkers and clinical outcomes, this review aims to summarize the current literature considering [...] Read more.
Circulating biomarkers have been recently investigated among patients undergoing endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). Considering the plethora of small descriptive studies reporting potential associations between biomarkers and clinical outcomes, this review aims to summarize the current literature considering both the treated disease (post EVAR) and the untreated disease (AAA before EVAR). All studies describing outcomes of tissue biomarkers in patients undergoing EVAR and in patients with AAA were included, and references were checked for additional sources. In the EVAR scenario, circulating interleukin-6 (IL-6) is a marker of inflammatory reaction which might predict postoperative morbidity; cystatin C is a promising early marker of post-procedural acute kidney injury; plasma matrix metalloproteinase-9 (MMP-9) concentration after 3 months from EVAR might help in detecting post-procedural endoleak. This review also summarizes the current gaps in knowledge and future direction of this field of research. Among markers used in patients with AAA, galectin and granzyme appear to be promising and should be carefully investigated even in the EVAR setting. Larger prospective trials are required to establish and evaluate prognostic models with highest values with these markers. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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20 pages, 369 KiB  
Review
Recent Updates and Advances in Winiwarter-Buerger Disease (Thromboangiitis Obliterans): Biomolecular Mechanisms, Diagnostics and Clinical Consequences
by Bahare Fazeli, Daniela Ligi, Shayan Keramat, Rosanna Maniscalco, Hiva Sharebiani and Ferdinando Mannello
Diagnostics 2021, 11(10), 1736; https://doi.org/10.3390/diagnostics11101736 - 22 Sep 2021
Cited by 12 | Viewed by 4859
Abstract
Thromboangiitis obliterans (TAO) or Buerger’s disease is a segmental inflammatory, thrombotic occlusive peripheral vascular disease with unknown aetiology that usually involves the medium and small-sized vessels of young male smokers. Due to its unknown aetiology and similarities with atherosclerosis and vasculitis, TAO diagnosis [...] Read more.
Thromboangiitis obliterans (TAO) or Buerger’s disease is a segmental inflammatory, thrombotic occlusive peripheral vascular disease with unknown aetiology that usually involves the medium and small-sized vessels of young male smokers. Due to its unknown aetiology and similarities with atherosclerosis and vasculitis, TAO diagnosis is still challenging. We aimed to review the status of biomolecular and laboratory para-clinical markers in TAO compared to atherosclerosis and vasculitis. We reported that, although some biomarkers might be common in TAO, atherosclerosis, and vasculitis, each disease occurs through a different pathway and, to our knowledge, there is no specific and definitive marker for differentiating TAO from atherosclerosis or vasculitis. Our review highlighted that pro-inflammatory and cell-mediated immunity cytokines, IL-33, HMGB1, neopterin, MMPs, ICAM1, complement components, fibrinogen, oxidative stress, NO levels, eNOS polymorphism, adrenalin and noradrenalin, lead, cadmium, and homocysteine are common markers. Nitric oxide, MPV, TLRs, MDA, ox-LDL, sST2, antioxidant system, autoantibodies, and type of infection are differential markers, whereas platelet and leukocyte count, haemoglobin, lipid profile, CRP, ESR, FBS, creatinine, d-dimer, hypercoagulation activity, as well as protein C and S are controversial markers. Finally, our study proposed diagnostic panels for laboratory differential diagnosis to be considered at first and in more advanced stages. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases 2.0)
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