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Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 22553

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Prof. Dr. Julia Bujan

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: artery; histology; vascular medicine
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Prof. Dr. Melchor Álvarez de Mon

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1. Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
2. Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias, (CIBEREHD), 28806 Alcala de Henares, Spain
Interests: immune system; systemic diseases; semiology; cytokines; translational medicine
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Dr. Miguel Ortega

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: vascular diseases; artery; venous disease; venous hypertension; heart; lymph; diabetes; immune system; translational medicine
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Dr. Miguel Ángel Alvarez de Mon

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: personalized medicine; clinical medicine; new therapies; medical–patient relationship
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Prof. Dr. Jorge Monserrat

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: inflammation; T, B and NK cells; monocytes and dendritic cells functions applied to immune system and infection (multiorgan failure syndrome, COVID-19); autoimmunity (rheumatoid arthritis and lupus); cancer (leukemia and lung cancer); hepatology; fibromyalgia and mayor depression; expert in flow cytometry
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Prof. Dr. Natalio García-Honduvilla

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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: tissue engineering; vascular medicine; targeted therapies; translational medicine
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Special Issue Information

Dear Colleagues,

Chronic vascular diseases are a clinical medicine problem that consumes a large amount of economic resources and that most affects the quality of life of the patient. In this sense, biological and medical research has advanced to develop new personalized strategies that allow a better approach to the patient. The connection between research and clinical practice is essential to achieve effective and efficient knowledge generation.

For this reason, investigations have to understand all the aspects that allow us to know the state of the tissue, the histology, and the systemic repercussions. Tissue engineering therapies are necessary to allow an effective and integrative repair of tissues damaged by these diseases. All this allows the development of personalized medicine.

Therefore, the aim of this Special Issue is to allow biological and medical research to play a key role in chronic vascular diseases for a better and personalized therapy for these patients.

Prof. Dr. Julia Bujan
Prof. Dr. Melchor Alvarez-Mon
Dr. Miguel Angel Ortega
Dr. Miguel A Alvarez-Mon
Prof. Dr. Jorge Monserrat
Dr. Natalio García-Honduvilla
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

vascular medicine
tissue engineering
histopathology
injury repair
varicose vein
phlebology
artery
targeted therapies
new personalized interventionist approaches

Published Papers (10 papers)

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Research

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14 pages, 2261 KiB

Open AccessFeature PaperArticle

Deteriorated Vascular Homeostasis in Hypertension: Experimental Evidence from Aorta, Brain, and Pancreatic Vasculature

by Hadi Taghizadeh, Ali Taghizadehghalehjoughi, Serkan Yildirim, Mustafa Ozkaraca, Sidika Genc, Yesim Yeni, Muhammed Yasser Mokresh, Ahmet Hacimuftuoglu, Aristidis Tsatsakis and Konstantinos Tsarouhas

J. Pers. Med. 2022, 12(10), 1602; https://doi.org/10.3390/jpm12101602 - 28 Sep 2022

Cited by 2 | Viewed by 1724

Abstract

Hypertension, as a primary risk factor for many fatal disorders, is prevalent in the elderly. There is wide literature on hypertension dealing with its biological and/or biochemical aspects; however, limited research is available on the multifactorial nature of hypertension from a mechanobiological standpoint. This study intended to study in parallel histopathological alterations and deviated protein expressions with the mechanical behavior of the hypertensive tissues. The Goldblatt (2K1C) method was chosen for induction of renovascular hypertension in rabbits. The microstructural and immunohistological characteristics of the aortic, pancreatic, and brain vasculature were investigated. The mechanical properties of the aortic tissue were also evaluated using biaxial tensile tests. Our findings indicated severe hypertrophy of the hypertensive vessels and declined content of intact smooth muscle cells. Most of the collagen I content of the wall was compromised and less functional type III collagen was highly expressed. Reversed collagen I to collagen III ratio was the main contributor to the hypertrophic and less stiff hypertensive vessel walls. The multifactorial nature of hypertension is illustrated, and smooth muscle cell detachment is identified as the sign of described degenerative cascades all along the arterial tree. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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11 pages, 600 KiB

Open AccessArticle

Venous Segmental Flow Changes after Superficial Venous Intervention Demonstrating by Quantitative Phase-Contrast Magnetic Resonance Analysis: Preliminary Data from a Longitudinal Cohort Study

by Chien-Wei Chen, Yuan-Hsi Tseng, Chih-Chen Kao, Yeh Giin Ngo, Chung-Yuan Lee, Teng-Yao Yang, Yu-Hui Lin and Yao-Kuang Huang

J. Pers. Med. 2022, 12(6), 1000; https://doi.org/10.3390/jpm12061000 - 19 Jun 2022

Viewed by 1510

Abstract

The effects of superficial venous intervention on hemodynamics can be quantified using two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI). Twelve patients received pre- and postintervention 2D PC-MRI analysis using quantitative hemodynamic parameters. Fifteen healthy volunteers served as controls. The 2D PC-MRI results of the target limbs (limbs scheduled for intervention for venous reflux) differed from those of the controls in terms of stroke volume (SV), forward flow volume (FFV), absolute stroke volume (ASV), and mean flux (MF) in all venous segments. The velocity time integral (VTI) and mean velocity (MV) of the popliteal vein (PV) segments were similar between the target limbs and controls preoperatively. After intervention, the target limbs exhibited an increase in VTI and MV in the femoral vein (FV) and PV segments. We compared the target and nontreated limbs of the individual patients preoperatively and postoperatively to minimalize individual bias. All QFlow parameter ratios in the FV segment increased after venous intervention (VTI, p = 0.025; MV, p = 0.024). In the PV segment, FFV and ASV increased significantly (p = 0.035 and 0.024, respectively). After interventions, the volume (FFV and ASV) of the PV segment and the efficiency (VTI and MV) of the FV segment significantly increased. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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24 pages, 13237 KiB

Open AccessArticle

Numerical Assessment of the Risk of Abnormal Endothelialization for Diverter Devices: Clinical Data Driven Numerical Study

by Denis Tikhvinskii, Julia Kuianova, Dmitrii Kislitsin, Kirill Orlov, Anton Gorbatykh and Daniil Parshin

J. Pers. Med. 2022, 12(4), 652; https://doi.org/10.3390/jpm12040652 - 18 Apr 2022

Cited by 3 | Viewed by 2022

Abstract

Numerical modeling is an effective tool for preoperative planning. The present work is devoted to a retrospective analysis of neurosurgical treatments for the occlusion of cerebral aneurysms using flow-diverters and hemodynamic factors affecting stent endothelization. Several different geometric approaches have been considered for virtual flow-diverters deployment. A comparative analysis of hemodynamic parameters as a result of computational modeling has been carried out basing on the four clinical cases: one successful treatment, one with no occlusion and two with in stent stenosis. For the first time, a quantitative assessment of both: the limiting magnitude of shear stresses that are necessary for the occurrence of in stent stenosis (MaxWSS > 1.23) and for conditions in which endothelialization is insufficiently active and occlusion of the cervical part of the aneurysm does not occur (MaxWSS < 1.68)—has been statistacally proven (p < 0.01). Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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15 pages, 2778 KiB

Open AccessArticle

Histological Profiling of the Human Umbilical Cord: A Potential Alternative Cell Source in Tissue Engineering

by Cristina Blanco-Elices, Jesús Chato-Astrain, Alberto González-González, David Sánchez-Porras, Víctor Carriel, Ricardo Fernández-Valadés, María del Carmen Sánchez-Quevedo, Miguel Alaminos and Ingrid Garzón

J. Pers. Med. 2022, 12(4), 648; https://doi.org/10.3390/jpm12040648 - 18 Apr 2022

Cited by 5 | Viewed by 2743

Abstract

The embryonic development of the human umbilical cord (hUC) is complex, and different regions can be identified in this structure. The aim of this work is to characterize the hUC at in situ and ex vivo levels to stablish their potential use in vascular regeneration. Human umbilical cords were obtained and histologically prepared for in the situ analysis of four hUC regions (intervascular—IV, perivascular—PV, subaminoblastic—SAM, and Wharton’s jelly—WH), and primary cell cultures of mesenchymal stem cells (hUC-MSC) isolated from each region were obtained. The results confirmed the heterogeneity of the hUC, with the IV and PV zones tending to show the higher in situ expression of several components of the extracellular matrix (collagens, proteoglycans, and glycosaminoglycans), vimentin, and MSC markers (especially CD73), although isolation and ex vivo culture resulted in a homogeneous cell profile. Three vascular markers were positive in situ, especially vWF, followed by CD34 and CD31, and isolation and culture revealed that the region associated with the highest expression of vascular markers was IV, followed by PV. These results confirm the heterogeneity of the hUC and the need for selecting cells from specific regions of the hUC for particular applications in tissue engineering. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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11 pages, 1233 KiB

Open AccessArticle

Endoglin and Other Angiogenesis Markers in Recurrent Varicose Veins

by Francisco S. Lozano Sánchez, José A. Carnicero Martínez, Lucía Méndez-García, M. Begoña García-Cenador and Miguel Pericacho

J. Pers. Med. 2022, 12(4), 528; https://doi.org/10.3390/jpm12040528 - 25 Mar 2022

Cited by 2 | Viewed by 1955

Abstract

Background: Surgery on varicose veins (crossectomy and stripping) may lead to recurrence, with clinical and socioeconomic repercussions. The etiopathogenesis of varicose veins has yet to be fully understood. Objective: Study the expression of endoglin and other molecules involved in the neovascularisation process in patients suffering from this disease. Methods: Total of 43 patients that have undergone surgery for varicose veins (24 primary and 19 recurrent). Endoglin and other molecules were identified on the venous wall (proximal -saphenofemoral junction- and distal), via real-time RT-PCR, and in serum, via ELISA: endoglin (Eng), vascular endothelial growth factor (VEGF-A), its receptors 1 and 2 (VEGFR1 or FLT1), (VEGFR2 or FLK), and the hypoxia-inducible factor (HIF-1A). All the patients signed a consent form. Results: The recurrent group recorded a higher expression of Eng, VEGF-A, VEGFR1, and VEGFR2 at the level of proximal venous wall compared to the primary group. HIF-1A did not record any differences. As regards the determination of the distal venous wall, no markers recorded differences between the groups. Among the serum determinations, only sFLT1 recorded a significant drop among the patients with recurrent varicose veins. Conclusions: Patients with recurrent varicose veins record a higher expression of endoglin and other markers of angiogenesis in proximal veins. Endoglin in the blood (sEng) serves no apparent purpose in recurrent varicose veins. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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11 pages, 2030 KiB

Open AccessEditor’s ChoiceArticle

Chronic Venous Disease in Pregnant Women Causes an Increase in ILK in the Placental Villi Associated with a Decrease in E-Cadherin

by Miguel A. Ortega, Chen Chaowen, Oscar Fraile-Martinez, Cielo García-Montero, Miguel A. Saez, Iris Cruza, Claude Pereda-Cerquella, Miguel Angel Alvarez-Mon, Luis G. Guijarro, Yuliia Fatych, César Menor-Salván, Melchor Alvarez-Mon, Juan De Leon-Luis, Julia Buján, Natalio Garcia-Honduvilla, Coral Bravo and Angel Asúnsolo-del-Barco

J. Pers. Med. 2022, 12(2), 277; https://doi.org/10.3390/jpm12020277 - 14 Feb 2022

Cited by 7 | Viewed by 2097

Abstract

Chronic venous disease (CVD) is a multifactorial vascular disorder frequently manifested in lower limbs in the form of varicose veins (VVs). Women are a vulnerable population for suffering from CVD, especially during pregnancy, when a plethora of changes occur in their cardiovascular system. Previous studies have indicated a worrisome association between CVD in pregnancy with the placental structure and function. Findings include an altered cellular behavior and extracellular matrix (ECM) composition. Integrin-linked kinase (ILK) is a critical molecule involved in multiple physiological and pathological conditions, and together with cadherins, is essential to mediate cell to ECM and cell to cell interplay, respectively. Thus, the aim of this study was to evaluate the implication of ILK and a set of cadherins (e-cadherin, cadherin-6 and cadherin-17) in placentas of women with CVD in order to unravel the possible pathophysiological role of these components. Gene expression (RT-qPCR) and protein expression (immunohistochemistry) studies were performed. Our results show a significant increase in the gene and protein expression of ILK, cadherin-6 and cadherin-17 and a decrease of e-cadherin in the placenta of women with CVD. Overall, this work shows that an abnormal expression of ILK, e-cadherin, cadherin-6 and cadherin-17 may be implicated in the pathological changes occurring in the placental tissue. Further studies should be conducted to determine the possible associations of these changes with maternal and fetal well-being. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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18 pages, 9575 KiB

Open AccessArticle

Contribution of the Elastic Component and Venous Wall Arterialization in Patients with Venous Reflux

by Miguel A. Ortega, Oscar Fraile-Martínez, Cielo García-Montero, Fernando Ruiz-Grande, Miguel Angel Álvarez-Mon, Jorge Monserrat, Luis G. Guijarro, Santiago Coca, Melchor Álvarez-Mon, Julia Bujan, Natalio García-Honduvilla and Miguel A. Sáez

J. Pers. Med. 2022, 12(2), 260; https://doi.org/10.3390/jpm12020260 - 10 Feb 2022

Cited by 3 | Viewed by 1649

Abstract

Chronic venous disease (CVeD) is defined as a set of disorders affecting the venous system mainly manifested in the form of varicose veins. CVeD is characterized by a sustained venous hypertension, leading to a plethora of functional and structural changes in the vein that may cause valve incompetence and pathologic reflux. In turn, venous reflux aggravates the venous hypertension and enhances the progression of CVeD into the most advanced stages. Previous studies have proposed that there are several alterations in the venous wall preceding the valve dysfunction and venous reflux. Besides, it has also been identified that young patients with CVeD present premature aging and changes in the venous wall composition that may be related to the presence of venous reflux. In this context, the aim of the present study is to examine the possible pathophysiological role of elastic fibers and their precursors in the venous wall of patients with reflux in comparison to those without reflux, considering the variable age in both groups (<50 years and ≥50 years). We performed immunohistochemical and quantitative polymerase chain reaction (PCR) in order to assess the protein and gene expression of tropoelastin, fibrillin-1, fibulins 4 and 5, lysyl oxidase and lysyl oxidase like 1, respectively. In parallel, we assessed the elastin content through histological techniques (orcein stain) in this group of patients. Our results show significant changes in elastic fibers and their precursors in young patients with pathologic reflux when compared with elder patients with reflux and young patients without reflux. These variations suggest that the venous system of young patients with venous reflux appears to present an enhanced dynamism and arterialization of the venous wall, which may be associated with a premature aging and pathological environment of the tissue. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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14 pages, 3033 KiB

Open AccessArticle

A Novel Tool for a Challenging Disease: Stasis Leg Ulcers Assessed Using QFlow in Triggered Angiography Noncontrast Enhanced Magnetic Resonance Imaging

by Chien-Wei Chen, Yueh-Fu Fang, Yuan-Hsi Tseng, Min-Yi Wong, Yu-Hui Lin, Yin-Chen Hsu, Bor-Shyh Lin and Yao-Kuang Huang

J. Pers. Med. 2021, 11(9), 857; https://doi.org/10.3390/jpm11090857 - 28 Aug 2021

Cited by 4 | Viewed by 2409

Abstract

Imaging characteristics of stasis leg ulcers (SLUs) are not easily demonstrated through existing diagnostic tools. Early diagnosis and treatment are crucial. This pilot study was conducted to assess the quantitative flow (QFlow) in triggered angiography noncontrast enhanced (TRANCE) magnetic resonance imaging (MRI) to identify the hemodynamics of victims with stasis leg ulcers (SLUs). This study included 33 patients with SLUs and 14 healthy controls (HC). The 33 patients with SLUs were divided into a reflux (15 patients) and a nonreflux group (18 patients). QFlow was done in the reflux, the nonreflux, and the HC. The stroke volume (SV), forward flow volume (FFV), absolute flow volume (AFV), mean flow (MF), and mean velocity (MV) were higher in the reflux than in the HC group in most segments, namely the external iliac vein (EIV), popliteal vein (PV), and great saphenous vein (GSV) (SV, p = 0.008; FFV, p = 0.008; absolute stroke volume (ASV), p = 0.008; MF, p = 0.002; MV, p = 0.009). No differences in the QFlow patterns were found in the GSV segment between the nonreflux group and the HC. Excellent performance in discriminating SLU with superficial venous reflux was reported for SV in the EIV and the PV (area under the curve (AUC) = 0.851 and 0.872), FFV in the EIV and PV (AUC = 0.854 and 0.869), ASV in the EIV and PV (AUC = 0.848 and 0.881), and MF in the EIV and PV (AUC = 0.866 and 0.868). The cutoff levels of SV/FFV/ASV/MF in the EIV/FV/PV/GSV for discriminating the SLU with superficial venous reflux were identified (p < 0.005). In conclusion, SLUs present different QFlow patterns by different etiology. The QFlow parameters of all vessel segments were higher in the morbid limbs of the reflux group than HC. The GSV segment of the nonreflux group displayed a pattern like the HC. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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14 pages, 2826 KiB

Open AccessArticle

Superficial Venous Reflux Intervention Guided by Triggered Angiography Non-Contrast-Enhanced Sequence Magnetic Resonance Imaging: Different QFlow Pattern from Health Controls

by Chien-Wei Chen, Yuan-Hsi Tseng, Yueh-Fu Fang, Min Yi Wong, Yu-Hui Lin and Yao-Kuang Huang

J. Pers. Med. 2021, 11(8), 751; https://doi.org/10.3390/jpm11080751 - 30 Jul 2021

Cited by 6 | Viewed by 1754

Abstract

(1) Background: To assess the effectiveness of triggered angiography non-contrast-enhanced (TRANCE)-magnetic resonance imaging (MRI) in superficial venous reflux and its difference from health controls. (2) Methods: Thirty patients underwent TRANCE MRI before surgical intervention of their superficial venous reflux of the legs. Ten healthy volunteers were included as a control. (3) Results: TRANCE MRI involves the major tributaries, thus enhances the additional ablations in 20% of patients. QFlow pattern of superficial venous reflux (QFlow GSV/PV MF ratio > 1) was compared with the duplex scan (SFJ reflux) using Cohen’s kappa coefficient at 0.967. The 30 morbid legs undergoing TRANCE MRI-guide interventions and the healthy volunteers’ legs on the same side were compared. The stroke volumes (SV) are higher in EIV (p = 0.021) in the left-leg-intervention group. The mean flux (MF) is higher in the EIV (p = 0.012) and trend of increasing in GSV segment (p = 0.087) in the left-leg-intervention group. The QFlow of 10 patients with right leg intervention are higher in GSV in the right-leg-intervention group (SV p = 0.002; FFV p = 0.001; MF p = 0.001). QFlow data is shown for all legs for superficial venous intervention with GSV/PV (MF) ratio > 1. (4) Conclusions: Typical figures in QFlow (GSV/PV MF ratio > 1) could be observed in the morbid limbs but not in the controls. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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Review

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11 pages, 1127 KiB

Open AccessReview

Endothelial Senescence and the Chronic Vascular Diseases: Challenges and Therapeutic Opportunities in Atherosclerosis

by Rafael Ramírez, Noemi Ceprian, Andrea Figuer, Gemma Valera, Guillermo Bodega, Matilde Alique and Julia Carracedo

J. Pers. Med. 2022, 12(2), 215; https://doi.org/10.3390/jpm12020215 - 04 Feb 2022

Cited by 9 | Viewed by 3343

Abstract

Atherosclerosis is probably one of the paradigms of disease linked to aging. Underlying the physiopathology of atherosclerosis are cellular senescence, oxidative stress, and inflammation. These factors are increased in the elderly and from chronic disease patients. Elevated levels of oxidative stress affect cellular function and metabolism, inducing senescence. This senescence modifies the cell phenotype into a senescent secretory phenotype. This phenotype activates immune cells, leading to chronic systemic inflammation. Moreover, due to their secretory phenotype, senescence cells present an increased release of highlighted extracellular vesicles that will change nearby/neighborhood cells and paracrine signaling. For this reason, searching for specific senescent cell biomarkers and therapies against the development/killing of senescent cells has become relevant. Recently, senomorphic and senolityc drugs have become relevant in slowing down or eliminating senescence cells. However, even though they have shown promising results in experimental studies, their clinical use is still yet to be determined. Full article

(This article belongs to the Special Issue Chronic Vascular Disease and Personalized Medicine: Unraveling New Horizons)

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